Is EFCAB7 p.Pro18Leu (c.53C>T) pathogenic?

EFCAB7 p.Pro18Leu (c.53C>T) is classified Likely benign in EFCAB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0567); Very rare (popmax 0.00136%, afr).

How common is EFCAB7 p.Pro18Leu (c.53C>T) in the general population?

EFCAB7 p.Pro18Leu (c.53C>T) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about EFCAB7 p.Pro18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

EFCAB7 p.Pro18Leu

c.53C>T · VCV4247014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.17	GERP -3.5, phastCons 0.016
Regional constraint	o/e 0.87	unconstrained · MANE · 47 kb · p 0.00062 · regional, not allelic
Overall
CADD	0.141	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 0.00136% African / African-American · 1/73,454 alleles

Overall 0.000188% 3/1,596,504 alleles · very rare exomes 3/1,444,274 · genomes 0/152,230 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,842
African / African-Americangrpmax	0.00136%	73,454
European (non-Finnish)	8.5e-05%	1,176,230

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EFCAB7
Protein: p.Pro18Leu
Coding: c.53C>T
MANE Select: NM_032437
Type: single nucleotide variant
Location: chr1:63525625 (GRCh38)

Full EFCAB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/efcab7-p-pro18leu (accessed [today's date]).

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