Is OR51E2 p.Ser32Pro (c.94T>C) pathogenic?

OR51E2 p.Ser32Pro (c.94T>C) is classified Uncertain significance in OR51E2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). AlphaMissense: ambiguous (0.4198); Rare (popmax 0.115%, mid).

How common is OR51E2 p.Ser32Pro (c.94T>C) in the general population?

OR51E2 p.Ser32Pro (c.94T>C) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about OR51E2 p.Ser32Pro (c.94T>C)?

AlphaMissense predicts ambiguous (score 0.4198) — an in-silico prediction, not a clinical call.

OR51E2 p.Ser32Pro

c.94T>C · rs148831989 · VCV2399447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4198 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4198	ambiguous
REVEL	0.145	moderately benign-leaning
SaProt	LLR -9.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 0.76, phastCons 0.87
Regional constraint	o/e 1.17	unconstrained · MANE · 959 bp · p 0.00066 · regional, not allelic
Overall
CADD	18.3	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 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.053%

Overall 0.0482% 778/1,614,192 alleles · rare exomes 732/1,461,890 · genomes 46/152,302 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
European (non-Finnish)	0.058%	1,723
South Asian	0.0538%	1,859
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.00833%	12,004
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
African / African-American	0.00533%	18,763
Finnishnot grpmax-eligible	0.00156%	64,042

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: OR51E2
Protein: p.Ser32Pro
Coding: c.94T>C
MANE Select: NM_030774
dbSNP: rs148831989
Type: single nucleotide variant
Location: chr11:4682618 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.97 · 1 PDB
Residue 32: an α-helix

Full OR51E2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OR51E2 p.Ala236Asp Uncertain significance ★ ⚠ same type
OR51E2 p.Ala304Val Uncertain significance ★ ⚠ same type
OR51E2 p.Ala71Gly Uncertain significance ★ ⚠ same type
OR51E2 p.Ala82Thr Uncertain significance ★ ⚠ same type
OR51E2 p.Ala95Gly Uncertain significance ★ ⚠ same type
OR51E2 p.Ala9Thr Uncertain significance ★ ⚠ same type
OR51E2 p.Arg150His Uncertain significance ★ ⚠ same type
OR51E2 p.Arg233Gly 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/or51e2-p-ser32pro (accessed [today's date]).

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