Is SI p.Ser767Phe (c.2300C>T) pathogenic?

SI p.Ser767Phe (c.2300C>T) is classified Uncertain significance in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). AlphaMissense: likely benign (0.2978); Very rare (popmax 0.00167%, amr).

How common is SI p.Ser767Phe (c.2300C>T) in the general population?

SI p.Ser767Phe (c.2300C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SI p.Ser767Phe (c.2300C>T)?

AlphaMissense predicts likely benign (score 0.2978) — an in-silico prediction, not a clinical call.

SI p.Ser767Phe

c.2300C>T · rs752951766 · VCV1938590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2978	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,754 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000267%

Overall 0.000634% 10/1,578,488 alleles · very rare exomes 10/1,426,332 · genomes 0/152,156 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,754
European (non-Finnish)	0.000783%	127,729

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.Ser767Phe
Coding: c.2300C>T
MANE Select: NM_001041
dbSNP: rs752951766
Type: single nucleotide variant
Location: chr3:165039079 (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 767: the 'isomaltase' region; a turn

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

Similar variants

SI p.Ser767= Uncertain significance ★ same residue
SI c.2426+1G>A Likely pathogenic ★★ same type
SI c.2737-2A>G Likely pathogenic ★★ same type
SI c.2893-1G>A Likely pathogenic ★★ same type
SI c.3099+1G>C Likely pathogenic ★★ same type
SI c.3521-1G>T Likely pathogenic ★★ same type
SI c.373+1G>A Likely pathogenic ★★ same type
SI c.4575+2T>C Likely pathogenic ★★ same type

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-ser767phe (accessed [today's date]).

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