Is SGMS2 p.Pro336= (c.1008G>A) pathogenic?

SGMS2 p.Pro336= (c.1008G>A) is classified Benign/Likely benign in SGMS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Low-frequency (popmax 1.17%, afr).

How common is SGMS2 p.Pro336= (c.1008G>A) in the general population?

SGMS2 p.Pro336= (c.1008G>A) is low-frequency (popmax 1.17%, afr) (gnomAD).

SGMS2 p.Pro336=

c.1008G>A · rs34576975 · VCV2053985

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

⚠ 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 -4.5
Overall
CADD	1.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.17% African / African-American · 878/74,976 alleles

Filtering AF 1.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0635% 1,025/1,613,908 alleles · low-frequency exomes 507/1,461,760 · genomes 518/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	85
Admixed American	0.0817%	1,224
Remaining individualsnot grpmax-eligible	0.064%	1,562
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.00458%	21,851
Finnishnot grpmax-eligible	0.00156%	63,960
South Asian	0.0011%	91,076

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.Pro336=
Coding: c.1008G>A
MANE Select: NM_001375905
dbSNP: rs34576975
Type: single nucleotide variant
Location: chr4:107910463 (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-pro336 (accessed [today's date]).

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