Is SGMS2 p.Val91Phe (c.271G>T) pathogenic?

SGMS2 p.Val91Phe (c.271G>T) is classified Uncertain significance in SGMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.0887); Very rare (popmax 0.00534%, afr); Associated with SGMS2-related disorder.

What condition is associated with SGMS2 p.Val91Phe (c.271G>T)?

SGMS2 p.Val91Phe (c.271G>T) is associated with SGMS2-related disorder (ClinVar).

How common is SGMS2 p.Val91Phe (c.271G>T) in the general population?

SGMS2 p.Val91Phe (c.271G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about SGMS2 p.Val91Phe (c.271G>T)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

SGMS2 p.Val91Phe

c.271G>T · rs147662224 · VCV2633304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SGMS2-related disorder

⚠ 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	0.0887	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -5.79	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	16.98	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 0.00534% African / African-American · 4/74,884 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,613,802 alleles · very rare exomes 4/1,461,690 · genomes 3/152,112 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,721
Admixed American	0.005%	19,985

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.Val91Phe
Coding: c.271G>T
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

Disease context

SGMS2-related disorder

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-val91phe (accessed [today's date]).

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