Is SGMS2 p.Val91= (c.273C>T) pathogenic?

SGMS2 p.Val91= (c.273C>T) is classified Likely benign in SGMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). Ultra-rare (popmax 0.0362%, sas).

How common is SGMS2 p.Val91= (c.273C>T) in the general population?

SGMS2 p.Val91= (c.273C>T) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

SGMS2 p.Val91=

c.273C>T · VCV4738233

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.66	GERP -1.9, phastCons 0.13
Overall
CADD	3.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% South Asian · 33/91,084 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00204% 33/1,614,008 alleles · ultra-rare exomes 32/1,461,708 · genomes 1/152,300 · joint denominator

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.Val91=
Coding: c.273C>T
MANE Select: NM_001375905
Type: single nucleotide variant
Location: chr4:107895826 (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-val91 (accessed [today's date]).

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