Is EPS15 p.His287Arg (c.860A>G) pathogenic?

EPS15 p.His287Arg (c.860A>G) is classified Uncertain significance in EPS15 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: ambiguous (0.3889); Very rare (popmax 0.00661%, nfe).

How common is EPS15 p.His287Arg (c.860A>G) in the general population?

EPS15 p.His287Arg (c.860A>G) is very rare (popmax 0.00661%, nfe) (gnomAD).

What do computational predictors say about EPS15 p.His287Arg (c.860A>G)?

AlphaMissense predicts ambiguous (score 0.3889) — an in-silico prediction, not a clinical call.

EPS15 p.His287Arg

c.860A>G · rs368133150 · VCV2512486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3889	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -12.74	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 163 kb · p 0.94 · regional, not allelic
Overall
CADD	26.4	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 0.00661% European (non-Finnish) · 78/1,179,932 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00489% 79/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,127
South Asian	0.0011%	91,082

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: EPS15
Protein: p.His287Arg
Coding: c.860A>G
MANE Select: NM_001981
dbSNP: rs368133150
Type: single nucleotide variant
Location: chr1:51444983 (GRCh38)
Gene constraint: LOEUF 0.849 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.60 · 13 PDB
Residue 287: the 'interaction with dab2' region; the eh 3 domain; the ef-hand 4 domain; an α-helix

Full EPS15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS15 p.Ala208Ser Uncertain significance ★ ⚠ same type
EPS15 p.Ala2Ser Uncertain significance ★ ⚠ same type
EPS15 p.Ala39Thr Uncertain significance ★ ⚠ same type
EPS15 p.Ala423Val Uncertain significance ★ ⚠ same type
EPS15 p.Ala4Thr Uncertain significance ★ ⚠ same type
EPS15 p.Ala560Ser Uncertain significance ★ ⚠ same type
EPS15 p.Ala613Gly Uncertain significance ★ ⚠ same type
EPS15 p.Ala667Thr 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/eps15-p-his287arg (accessed [today's date]).

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