Is EFHD2 p.Ala160Val (c.479C>T) pathogenic?

EFHD2 p.Ala160Val (c.479C>T) is classified Uncertain significance in EFHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely pathogenic (0.5954); Very rare (popmax 0.00223%, eas).

How common is EFHD2 p.Ala160Val (c.479C>T) in the general population?

EFHD2 p.Ala160Val (c.479C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EFHD2 p.Ala160Val (c.479C>T)?

AlphaMissense predicts likely pathogenic (score 0.5954) — an in-silico prediction, not a clinical call.

EFHD2 p.Ala160Val

c.479C>T · VCV4016562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5954	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -10.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,564 bp · p 0.13 · regional, not allelic
Overall
CADD	29.0	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 0.00223% East Asian · 1/44,816 alleles

Overall 0.000206% 3/1,459,082 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,816
Remaining individualsnot grpmax-eligible	0.0016%	62,356
European (non-Finnish)	8.48e-05%	1,179,026

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: EFHD2
Protein: p.Ala160Val
Coding: c.479C>T
MANE Select: NM_024329
Type: single nucleotide variant
Location: chr1:15427172 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.28 · 5 PDB
Residue 160: an α-helix; the ef-hand 2 domain

Full EFHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFHD2 p.Ala161Val Uncertain significance ★ ⚠ same type
EFHD2 p.Ala200Thr Uncertain significance ★ ⚠ same type
EFHD2 p.Ala37Val Uncertain significance ★ ⚠ same type
EFHD2 p.Ala44Val Uncertain significance ★ ⚠ same type
EFHD2 p.Ala45Thr Uncertain significance ★ ⚠ same type
EFHD2 p.Ala51Val Uncertain significance ★ ⚠ same type
EFHD2 p.Arg151Gln Uncertain significance ★ ⚠ same type
EFHD2 p.Arg176Cys 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/efhd2-p-ala160val (accessed [today's date]).

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