Is EPHA2 p.Arg950Pro (c.2849G>C) pathogenic?

EPHA2 p.Arg950Pro (c.2849G>C) is classified Uncertain significance in EPHA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.7605); Very rare (popmax 0.00989%, sas); Associated with Inborn genetic diseases.

What condition is associated with EPHA2 p.Arg950Pro (c.2849G>C)?

EPHA2 p.Arg950Pro (c.2849G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EPHA2 p.Arg950Pro (c.2849G>C) in the general population?

EPHA2 p.Arg950Pro (c.2849G>C) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about EPHA2 p.Arg950Pro (c.2849G>C)?

AlphaMissense predicts likely pathogenic (score 0.7605) — an in-silico prediction, not a clinical call.

EPHA2 p.Arg950Pro

c.2849G>C · VCV4249782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7605	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -4.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP -3.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 8,090 bp · p 1.5e-10 · regional, not allelic
Overall
CADD	28.7	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 0.00989% South Asian · 9/91,036 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.0018% 29/1,613,340 alleles · very rare exomes 26/1,461,584 · genomes 3/151,756 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,115
European (non-Finnish)	0.00161%	62,097
African / African-American	0.00134%	74,764

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: EPHA2
Protein: p.Arg950Pro
Coding: c.2849G>C
MANE Select: NM_004431
Type: single nucleotide variant
Location: chr1:16125297 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 950: the 'negatively regulates interaction with arhgef16' region; the sam domain

Full EPHA2 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

EPHA2 p.Arg950= Likely benign ★ same residue
EPHA2 p.Arg315Trp Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg560His Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg566His Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg677Cys Uncertain significance ★★ ⚠ same condition
EPHA2 p.Asp148Asn Uncertain significance ★★ ⚠ same condition
EPHA2 p.Asp888Asn Uncertain significance ★★ ⚠ same condition
EPHA2 p.Cys309Arg 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/epha2-p-arg950pro (accessed [today's date]).

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