Is EPHB3 p.Ala315Thr (c.943G>A) pathogenic?

EPHB3 p.Ala315Thr (c.943G>A) is classified Uncertain significance in EPHB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.1272); Rare (popmax 0.139%, sas).

How common is EPHB3 p.Ala315Thr (c.943G>A) in the general population?

EPHB3 p.Ala315Thr (c.943G>A) is rare (popmax 0.139%, sas) (gnomAD).

What do computational predictors say about EPHB3 p.Ala315Thr (c.943G>A)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

EPHB3 p.Ala315Thr

c.943G>A · rs141695759 · VCV3089675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.84, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 19 kb · p 2.4e-21 · regional, not allelic
Overall
CADD	23.6	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 0.139% South Asian · 127/91,048 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.0294% 474/1,613,676 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.139%	717
European (non-Finnish)	0.0276%	3,619
Remaining individualsnot grpmax-eligible	0.0192%	5,208
African / African-American	0.00666%	15,006
Admixed American	0.005%	19,997
Finnishnot grpmax-eligible	0.00157%	63,852

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: EPHB3
Protein: p.Ala315Thr
Coding: c.943G>A
MANE Select: NM_004443
dbSNP: rs141695759
Type: single nucleotide variant
Location: chr3:184575916 (GRCh38)
Gene constraint: LOEUF 0.435 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.62 · 4 PDB

Full EPHB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHB3 c.1748+4C>T Benign ★★ same type
EPHB3 p.Phe689= Benign ★★ same type
EPHB3 p.Pro438= Benign ★★ same type
EPHB3 p.Ala220Thr Uncertain significance ★ ⚠ same type
EPHB3 p.Ala229Val Uncertain significance ★ ⚠ same type
EPHB3 p.Ala332Val Uncertain significance ★ ⚠ same type
EPHB3 p.Ala442Glu Uncertain significance ★ ⚠ same type
EPHB3 p.Ala517Thr 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/ephb3-p-ala315thr (accessed [today's date]).

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