Is EFCAB3 p.Ser370Phe (c.1109C>T) pathogenic?

EFCAB3 p.Ser370Phe (c.1109C>T) is classified Benign in EFCAB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). AlphaMissense: likely benign (0.2458); Low-frequency (popmax 1.83%, afr).

How common is EFCAB3 p.Ser370Phe (c.1109C>T) in the general population?

EFCAB3 p.Ser370Phe (c.1109C>T) is low-frequency (popmax 1.83%, afr) (gnomAD).

What do computational predictors say about EFCAB3 p.Ser370Phe (c.1109C>T)?

AlphaMissense predicts likely benign (score 0.2458) — an in-silico prediction, not a clinical call.

EFCAB3 p.Ser370Phe

c.1109C>T · rs115800066 · VCV781326

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2458 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2458	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 33 kb · p 0.00011 · regional, not allelic
Overall
CADD	25.2	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 1.83% African / African-American · 1,370/75,040 alleles

Filtering AF 1.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.71%

Overall 0.0937% 1,512/1,613,954 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.83%	55
Admixed American	0.105%	953
Remaining individualsnot grpmax-eligible	0.104%	961
European (non-Finnish)	0.00119%	84,276

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.Ser370Phe
Coding: c.1109C>T
MANE Select: NM_173503
dbSNP: rs115800066
Type: single nucleotide variant
Location: chr17:62416121 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.80
Residue 370: a UniProt-annotated variant site (in)

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 c.-5G>A Uncertain significance ★ same type
EFCAB3 c.-8C>G Uncertain significance ★ same type
EFCAB3 p.Ala208Thr Uncertain significance ★ ⚠ same type
EFCAB3 p.Ala334Thr 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-ser370phe (accessed [today's date]).

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