Is EHBP1 p.Gln951Pro (c.2852A>C) pathogenic?

EHBP1 p.Gln951Pro (c.2852A>C) is classified Uncertain significance in EHBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.1611); Ultra-rare (popmax 0.0672%, eas).

How common is EHBP1 p.Gln951Pro (c.2852A>C) in the general population?

EHBP1 p.Gln951Pro (c.2852A>C) is ultra-rare (popmax 0.0672%, eas) (gnomAD).

What do computational predictors say about EHBP1 p.Gln951Pro (c.2852A>C)?

AlphaMissense predicts likely benign (score 0.1611) — an in-silico prediction, not a clinical call.

EHBP1 p.Gln951Pro

c.2852A>C · rs369412506 · VCV2592279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1611 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0672%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1611	likely benign
REVEL	0.461	indeterminate
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 45 kb · p 0.19 · regional, not allelic
Overall
CADD	24.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q1022P vs ClinVar Q951P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0672% East Asian · 30/44,670 alleles

Filtering AF 0.0483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0419%

Overall 0.00317% 51/1,606,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0672%	1,489
Remaining individualsnot grpmax-eligible	0.0306%	3,273
Admixed American	0.00168%	59,666
European (non-Finnish)	8.51e-05%	1,175,679

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: EHBP1
Protein: p.Gln951Pro
Coding: c.2852A>C
MANE Select: NM_001142616
dbSNP: rs369412506
Type: single nucleotide variant
Location: chr2:62993648 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.13 · 4 PDB

Full EHBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHBP1 c.1185+30064G>A Uncertain significance ★★ same type
EHBP1 c.2609-2750G>A Uncertain significance ★ ⚠ same type
EHBP1 c.2609-2755A>G Uncertain significance ★ ⚠ same type
EHBP1 c.2609-2762G>T Uncertain significance ★ ⚠ same type
EHBP1 c.635-674G>A Uncertain significance ★ ⚠ same type
EHBP1 c.635-679A>G Uncertain significance ★ ⚠ same type
EHBP1 c.635-688G>A Uncertain significance ★ ⚠ same type
EHBP1 c.635-718A>T 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/ehbp1-p-gln951pro (accessed [today's date]).

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