Is OSMR p.Thr276Ser (c.827C>G) pathogenic?

OSMR p.Thr276Ser (c.827C>G) is classified Uncertain significance in OSMR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1112); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with OSMR p.Thr276Ser (c.827C>G)?

OSMR p.Thr276Ser (c.827C>G) is associated with Inborn genetic diseases (ClinVar).

How common is OSMR p.Thr276Ser (c.827C>G) in the general population?

OSMR p.Thr276Ser (c.827C>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about OSMR p.Thr276Ser (c.827C>G)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

OSMR p.Thr276Ser

c.827C>G · VCV4626715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -1.3, phastCons 0.001
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.11 · regional, not allelic
Overall
CADD	14.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,932 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,058 alleles · very rare exomes 8/1,461,758 · genomes 0/152,300 · joint denominator

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: OSMR
Protein: p.Thr276Ser
Coding: c.827C>G
MANE Select: NM_003999
Type: single nucleotide variant
Location: chr5:38885472 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.07 · 1 PDB

Full OSMR 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

OSMR p.Ser866Ala Uncertain significance ★★ ⚠ same condition
OSMR p.Val662Ala Uncertain significance ★★ same condition
OSMR p.Val169Ile Benign/Likely benign ★★ same condition
OSMR p.Ala197Thr Uncertain significance ★ ⚠ same condition
OSMR p.Ala27Thr Uncertain significance ★ ⚠ same condition
OSMR p.Ala2Ser Uncertain significance ★ ⚠ same condition
OSMR p.Ala407Val Uncertain significance ★ ⚠ same condition
OSMR p.Ala537Thr 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/osmr-p-thr276ser (accessed [today's date]).

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