Is SGMS2 p.Thr232= (c.696G>A) pathogenic?

SGMS2 p.Thr232= (c.696G>A) is classified Benign in SGMS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 3.57%, afr).

How common is SGMS2 p.Thr232= (c.696G>A) in the general population?

SGMS2 p.Thr232= (c.696G>A) is low-frequency (popmax 3.57%, afr) (gnomAD).

SGMS2 p.Thr232=

c.696G>A · rs9998850 · VCV776009

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.57%, afr)

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 0.68	GERP -3.2, phastCons 0.25
Overall
CADD	8.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.57% African / African-American · 2,678/74,992 alleles

Filtering AF 3.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.41%

Overall 0.188% 3,034/1,613,870 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.57%	28
Remaining individualsnot grpmax-eligible	0.243%	411
Admixed American	0.237%	422
Middle Eastern	0.182%	551
South Asian	0.00549%	18,218
European (non-Finnish)	0.0039%	25,650

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.Thr232=
Coding: c.696G>A
dbSNP: rs9998850
Type: single nucleotide variant
Location: chr4:107903355 (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-thr232 (accessed [today's date]).

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