Is EFCAB7 p.Ser626Phe (c.1877C>T) pathogenic?

EFCAB7 p.Ser626Phe (c.1877C>T) is classified Uncertain significance in EFCAB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: likely benign (0.2926); Ultra-rare (popmax 0.08%, mid).

How common is EFCAB7 p.Ser626Phe (c.1877C>T) in the general population?

EFCAB7 p.Ser626Phe (c.1877C>T) is ultra-rare (popmax 0.08%, mid) (gnomAD).

What do computational predictors say about EFCAB7 p.Ser626Phe (c.1877C>T)?

AlphaMissense predicts likely benign (score 0.2926) — an in-silico prediction, not a clinical call.

EFCAB7 p.Ser626Phe

c.1877C>T · rs149784056 · VCV2226938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2926 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.08%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2926	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 47 kb · p 0.00062 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.08% Middle Eastern · 4/5,000 alleles

Filtering AF 0.0564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.051%

Overall 0.031% 464/1,495,646 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.08%	1,250
South Asian	0.0716%	1,398
European (non-Finnish)	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.0139%	7,197
Admixed American	0.00634%	15,774
African / African-American	0.00572%	17,468
Finnishnot grpmax-eligible	0.00161%	62,080

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.Ser626Phe
Coding: c.1877C>T
MANE Select: NM_032437
dbSNP: rs149784056
Type: single nucleotide variant
Location: chr1:63572503 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62

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

Similar variants

EFCAB7 p.Phe279Cys Uncertain significance ★★ same type
EFCAB7 p.Asp571Glu Benign ★★ same type
EFCAB7 p.Ser186Gly Benign ★★ same type
EFCAB7 p.Ala472Val Uncertain significance ★ ⚠ same type
EFCAB7 p.Ala9Thr Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg203Trp Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg461Gly Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg475Gly 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/efcab7-p-ser626phe (accessed [today's date]).

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