Is EPHA4 p.Asp617= (c.1851C>T) pathogenic?

EPHA4 p.Asp617= (c.1851C>T) is classified Likely benign in EPHA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Ultra-rare (popmax 0.0147%, afr).

How common is EPHA4 p.Asp617= (c.1851C>T) in the general population?

EPHA4 p.Asp617= (c.1851C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

EPHA4 p.Asp617=

c.1851C>T · VCV4743441

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -5.4
Overall
CADD	4.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,814 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00645% 104/1,613,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,801
European (non-Finnish)	0.00737%	13,562
Admixed American	0.00334%	29,981
South Asian	0.00329%	30,351
Remaining individualsnot grpmax-eligible	0.0016%	62,464

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: EPHA4
Protein: p.Asp617=
Coding: c.1851C>T
MANE Select: NM_004438
Type: single nucleotide variant
Location: chr2:221443530 (GRCh38)
Gene constraint: LOEUF 0.256 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.93 · 17 PDB

Full EPHA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA4 p.Ala321Thr Uncertain significance ★★ ⚠ same type
EPHA4 p.Ala852Val Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg209Cys Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg230Gln Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg466Gln Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg466Trp Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg486Gln Uncertain significance ★★ ⚠ same type
EPHA4 p.Arg573Trp 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/epha4-p-asp617 (accessed [today's date]).

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