Is SGMS2 p.Val91Ile (c.271G>A) pathogenic?

SGMS2 p.Val91Ile (c.271G>A) is classified Likely benign in SGMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.0633); Ultra-rare (popmax 0.049%, eas).

How common is SGMS2 p.Val91Ile (c.271G>A) in the general population?

SGMS2 p.Val91Ile (c.271G>A) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about SGMS2 p.Val91Ile (c.271G>A)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

SGMS2 p.Val91Ile

c.271G>A · rs147662224 · VCV1565957

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.4	GERP 0.014, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 15 kb · p 0.0049 · regional, not allelic
Overall
CADD	16.51	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 0.049% East Asian · 22/44,860 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00409% 66/1,613,920 alleles · ultra-rare exomes 47/1,461,690 · genomes 19/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,039
African / African-American	0.0227%	4,412
Middle Eastern	0.0165%	6,058
South Asian	0.0132%	7,590
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.000932%	107,265

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: SGMS2
Protein: p.Val91Ile
Coding: c.271G>A
MANE Select: NM_001375905
dbSNP: rs147662224
Type: single nucleotide variant
Location: chr4:107895824 (GRCh38)

Full SGMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/sgms2-p-val91ile (accessed [today's date]).

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