Is EFCAB3 p.Ala55= (c.165C>T) pathogenic?

EFCAB3 p.Ala55= (c.165C>T) is classified Likely benign in EFCAB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-06). Ultra-rare (popmax 0.02%, afr).

How common is EFCAB3 p.Ala55= (c.165C>T) in the general population?

EFCAB3 p.Ala55= (c.165C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

EFCAB3 p.Ala55=

c.165C>T · rs147289901 · VCV745055

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, 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 1.8, phastCons 1
Overall
CADD	13.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,986 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00093% 15/1,613,446 alleles · ultra-rare

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: EFCAB3
Protein: p.Ala55=
Coding: c.165C>T
MANE Select: NM_173503
dbSNP: rs147289901
Type: single nucleotide variant
Location: chr17:62391835 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.80
Residue 55: the ef-hand 1 domain

Full EFCAB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB3 c.34+6G>T Benign ★★ same type
EFCAB3 c.488+2T>C Benign ★★ same type
EFCAB3 p.Arg99Ter Benign/Likely benign ★★ same type
EFCAB3 p.Lys15Asn Benign ★★ same type
EFCAB3 p.Ser370Phe Benign ★★ same type
EFCAB3 c.-5G>A Uncertain significance ★ same type
EFCAB3 c.-8C>G Uncertain significance ★ same type
EFCAB3 p.Ala208Thr 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/efcab3-p-ala55 (accessed [today's date]).

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