Is SI p.Val15Phe (c.43G>T) pathogenic?

SI p.Val15Phe (c.43G>T) is classified Benign/Likely benign in SI (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.079); Common (popmax 30%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Val15Phe (c.43G>T)?

SI p.Val15Phe (c.43G>T) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How is Congenital sucrase-isomaltase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SI p.Val15Phe (c.43G>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

SI p.Val15Phe

Q: How common is SI p.Val15Phe (c.43G>T) in the general population?

SI p.Val15Phe (c.43G>T) is common (popmax 30%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.43G>T · rs9290264 · VCV344075

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 30%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.545	indeterminate
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.001	GERP 0.73, phastCons 0.001
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30% European (non-Finnish) · 343,513/1,146,932 alleles

Filtering AF 29.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.8%

Overall 27.9% 438,335/1,572,826 alleles · common exomes 399,079/1,421,376 · genomes 39,256/151,450 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	30%	3
Ashkenazi Jewishnot grpmax-eligible	28.5%	4
Finnishnot grpmax-eligible	26.9%	4
Remaining individualsnot grpmax-eligible	26.6%	4
Middle Eastern	26.5%	4
South Asian	24.7%	4
Amishnot grpmax-eligible	24%	4
African / African-American	21.8%	5
Admixed American	15.4%	6
East Asian	10.1%	10

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SI
Protein: p.Val15Phe
Coding: c.43G>T
MANE Select: NM_001041
dbSNP: rs9290264
Type: single nucleotide variant
Location: chr3:165075970 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB
Residue 15: a UniProt-annotated variant site (in)

Full SI gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital sucrase-isomaltase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital sucrase-isomaltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SI c.2426+1G>A Likely pathogenic ★★ same condition
SI c.2893-1G>A Likely pathogenic ★★ same condition
SI c.3099+1G>C Likely pathogenic ★★ same condition
SI c.3521-1G>T Likely pathogenic ★★ same condition
SI c.373+1G>A Likely pathogenic ★★ same condition
SI c.4575+2T>C Likely pathogenic ★★ same condition
SI c.4927-1G>A Likely pathogenic ★★ same condition
SI c.5248-2A>C Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/si-p-val15phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown