Is SGMS2 p.Ser304Pro (c.910T>C) pathogenic?

SGMS2 p.Ser304Pro (c.910T>C) is classified Uncertain significance in SGMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely pathogenic (0.642); Very rare (popmax 0.00136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SGMS2 p.Ser304Pro (c.910T>C)?

SGMS2 p.Ser304Pro (c.910T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SGMS2 p.Ser304Pro (c.910T>C) in the general population?

SGMS2 p.Ser304Pro (c.910T>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about SGMS2 p.Ser304Pro (c.910T>C)?

AlphaMissense predicts likely pathogenic (score 0.642) — an in-silico prediction, not a clinical call.

SGMS2 p.Ser304Pro

c.910T>C · rs1181486803 · VCV2541111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ 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	0.642	likely pathogenic
REVEL	0.074	moderately benign-leaning
SaProt	LLR -13.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 15 kb · p 0.0049 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,944 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,613,928 alleles · very rare exomes 15/1,461,704 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,030
European (non-Finnish)grpmax	0.00136%	73,746

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser304Pro
Coding: c.910T>C
MANE Select: NM_001375905
dbSNP: rs1181486803
Type: single nucleotide variant
Location: chr4:107910365 (GRCh38)

Full SGMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser304pro (accessed [today's date]).

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