Is OMD p.Arg336His (c.1007G>A) pathogenic?

OMD p.Arg336His (c.1007G>A) is classified Uncertain significance in OMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.4273); Ultra-rare (popmax 0.0978%, sas).

How common is OMD p.Arg336His (c.1007G>A) in the general population?

OMD p.Arg336His (c.1007G>A) is ultra-rare (popmax 0.0978%, sas) (gnomAD).

What do computational predictors say about OMD p.Arg336His (c.1007G>A)?

AlphaMissense predicts ambiguous (score 0.4273) — an in-silico prediction, not a clinical call.

OMD p.Arg336His

c.1007G>A · rs372233789 · VCV3204293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4273 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0978%, sas)

Computational evidence

Protein change
AlphaMissense	0.4273	ambiguous
REVEL	0.368	indeterminate
SaProt	LLR -8.79	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,403 bp · p 0.054 · regional, not allelic
Overall
CADD	31.0	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 0.0978% South Asian · 89/91,046 alleles

Filtering AF 0.0813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.00886% 143/1,613,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0978%	1,023
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.0133%	7,494
East Asian	0.00447%	22,391
European (non-Finnish)	0.00271%	36,866

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: OMD
Protein: p.Arg336His
Coding: c.1007G>A
MANE Select: NM_001012267 · reported on NM_005014
dbSNP: rs372233789
Type: single nucleotide variant
Location: chr9:92415411 (GRCh38)

Full OMD 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/omd-p-arg336his (accessed [today's date]).

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