Is SGMS2 p.Pro27= (c.81C>T) pathogenic?

SGMS2 p.Pro27= (c.81C>T) is classified Likely benign in SGMS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-13). Ultra-rare (popmax 0.0164%, mid).

How common is SGMS2 p.Pro27= (c.81C>T) in the general population?

SGMS2 p.Pro27= (c.81C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

SGMS2 p.Pro27=

c.81C>T · rs753098107 · VCV2900263

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

⚠ 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 -5.8	GERP -5.3
Overall
CADD	0.318	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00446% 72/1,613,812 alleles · ultra-rare exomes 62/1,461,708 · genomes 10/152,104 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00534%	18,718
European (non-Finnish)	0.00525%	19,031
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Pro27=
Coding: c.81C>T
MANE Select: NM_001375905
dbSNP: rs753098107
Type: single nucleotide variant
Location: chr4:107895634 (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-pro27 (accessed [today's date]).

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