Is OSM p.Ala172Thr (c.514G>A) pathogenic?

OSM p.Ala172Thr (c.514G>A) is classified Likely benign in OSM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.0056%, nfe).

How common is OSM p.Ala172Thr (c.514G>A) in the general population?

OSM p.Ala172Thr (c.514G>A) is very rare (popmax 0.0056%, nfe) (gnomAD).

What do computational predictors say about OSM p.Ala172Thr (c.514G>A)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

OSM p.Ala172Thr

c.514G>A · rs200481037 · VCV2210369

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0056%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.00	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 -4.7	GERP -2.6
Regional constraint	o/e 0.96	unconstrained · MANE · 2,913 bp · p 0.48 · regional, not allelic
Overall
CADD	0.001	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 0.0056% European (non-Finnish) · 66/1,178,604 alleles

Filtering AF 0.00452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00412%

Overall 0.00447% 72/1,611,632 alleles · very rare exomes 65/1,459,398 · genomes 7/152,234 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00801%	12,479
European (non-Finnish)grpmax	0.0056%	17,858
African / African-American	0.00133%	74,918

Remaining individuals 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: OSM
Protein: p.Ala172Thr
Coding: c.514G>A
MANE Select: NM_020530
dbSNP: rs200481037
Type: single nucleotide variant
Location: chr22:30264128 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 5 PDB
Residue 172: the 'disordered' region

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

Similar variants

OSM p.Gln97Ter Likely pathogenic ★ same type
OSM p.Ala101Asp Uncertain significance ★ ⚠ same type
OSM p.Ala120Val Uncertain significance ★ ⚠ same type
OSM p.Ala23Val Uncertain significance ★ ⚠ same type
OSM p.Ala26Val Uncertain significance ★ ⚠ same type
OSM p.Arg116Cys Uncertain significance ★ ⚠ same type
OSM p.Arg170Gln Uncertain significance ★ ⚠ same type
OSM p.Arg187Cys Uncertain significance ★ ⚠ same type

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/osm-p-ala172thr (accessed [today's date]).

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