Is EFCC1 p.Asp18His (c.52G>C) pathogenic?

EFCC1 p.Asp18His (c.52G>C) is classified Uncertain significance in EFCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely pathogenic (0.742); Very rare (popmax 0.00266%, sas).

How common is EFCC1 p.Asp18His (c.52G>C) in the general population?

EFCC1 p.Asp18His (c.52G>C) is very rare (popmax 0.00266%, sas) (gnomAD).

What do computational predictors say about EFCC1 p.Asp18His (c.52G>C)?

AlphaMissense predicts likely pathogenic (score 0.742) — an in-silico prediction, not a clinical call.

EFCC1 p.Asp18His

c.52G>C · rs1944761673 · VCV2591424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.742	likely pathogenic
REVEL	0.398	indeterminate
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.8	GERP 0.65, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.3 · regional, not allelic
Overall
CADD	27.5	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 0.00266% South Asian · 2/75,310 alleles

Filtering AF 0.000441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000165%

Overall 0.000227% 3/1,320,918 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00266%	37,655
Remaining individualsnot grpmax-eligible	0.00175%	57,044

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: EFCC1
Protein: p.Asp18His
Coding: c.52G>C
MANE Select: NM_001394090 · reported on NM_001377500
dbSNP: rs1944761673
Type: single nucleotide variant
Location: chr3:129001680 (GRCh38)

Full EFCC1 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/efcc1-p-asp18his (accessed [today's date]).

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