Is SOX5 p.Pro276Ser (c.826C>T) pathogenic?

SOX5 p.Pro276Ser (c.826C>T) is classified Likely benign in SOX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: ambiguous (0.4986); Very rare (popmax 0.00577%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SOX5 p.Pro276Ser (c.826C>T)?

SOX5 p.Pro276Ser (c.826C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SOX5 p.Pro276Ser (c.826C>T) in the general population?

SOX5 p.Pro276Ser (c.826C>T) is very rare (popmax 0.00577%, nfe) (gnomAD).

What do computational predictors say about SOX5 p.Pro276Ser (c.826C>T)?

AlphaMissense predicts ambiguous (score 0.4986) — an in-silico prediction, not a clinical call.

SOX5 p.Pro276Ser

c.826C>T · VCV3447510

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00577%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4986	ambiguous
REVEL	0.586	indeterminate
SaProt	LLR -7.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 303 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	29.4	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 0.00577% European (non-Finnish) · 68/1,179,248 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00434% 70/1,612,690 alleles · very rare exomes 67/1,460,552 · genomes 3/152,138 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00577%	17,342
African / African-American	0.00267%	37,416

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: SOX5
Protein: p.Pro276Ser
Coding: c.826C>T
MANE Select: NM_006940
Type: single nucleotide variant
Location: chr12:23665549 (GRCh38)
Gene constraint: LOEUF 0.204 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.95

Full SOX5 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

Similar variants

SOX5 p.Arg493Ter Pathogenic ★★ same condition
SOX5 p.Arg571Trp Pathogenic/Likely pathogenic ★★ same condition
SOX5 p.Gln208Ter Pathogenic ★★ same condition
SOX5 p.Ser538Ter Pathogenic ★★ same condition
SOX5 p.Ala328Thr Uncertain significance ★★ ⚠ same condition
SOX5 p.Arg593His Uncertain significance ★★ ⚠ same condition
SOX5 p.Asp377Asn Uncertain significance ★★ ⚠ same condition
SOX5 p.Asp45Glu Uncertain significance ★★ ⚠ same condition

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/sox5-p-pro276ser (accessed [today's date]).

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