Is SI p.Pro1200Ser (c.3598C>T) pathogenic?

SI p.Pro1200Ser (c.3598C>T) is classified Likely benign in SI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.2468); Rare (popmax 0.355%, afr).

How common is SI p.Pro1200Ser (c.3598C>T) in the general population?

SI p.Pro1200Ser (c.3598C>T) is rare (popmax 0.355%, afr) (gnomAD).

What do computational predictors say about SI p.Pro1200Ser (c.3598C>T)?

AlphaMissense predicts likely benign (score 0.2468) — an in-silico prediction, not a clinical call.

SI p.Pro1200Ser

c.3598C>T · rs78013297 · VCV1116797

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2468 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.355%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2468	likely benign
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -8.78	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	26.3	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 0.355% African / African-American · 266/74,900 alleles

Filtering AF 0.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.306%

Overall 0.0192% 309/1,612,768 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.355%	282
Admixed American	0.0267%	3,743
Remaining individualsnot grpmax-eligible	0.0208%	4,803
European (non-Finnish)	0.00119%	84,231

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.Pro1200Ser
Coding: c.3598C>T
MANE Select: NM_001041
dbSNP: rs78013297
Type: single nucleotide variant
Location: chr3:165017796 (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 1200: the 'sucrase' region

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

Similar variants

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
SI c.4927-1G>A 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-pro1200ser (accessed [today's date]).

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