Is EFCAB14 p.Ser429Phe (c.1286C>T) pathogenic?

EFCAB14 p.Ser429Phe (c.1286C>T) is classified Uncertain significance in EFCAB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0963); Absent from gnomAD v4.1.

How common is EFCAB14 p.Ser429Phe (c.1286C>T) in the general population?

EFCAB14 p.Ser429Phe (c.1286C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFCAB14 p.Ser429Phe (c.1286C>T)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

EFCAB14 p.Ser429Phe

c.1286C>T · VCV4663202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.01	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 3.5	GERP -0.82, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 40 kb · p 0.079 · regional, not allelic
Overall
CADD	21.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFCAB14
Protein: p.Ser429Phe
Coding: c.1286C>T
MANE Select: NM_014774
Type: single nucleotide variant
Location: chr1:46683326 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.45

Full EFCAB14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB14 p.Ala196Thr Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala393Thr Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala423Val Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala87Val Uncertain significance ★ same type
EFCAB14 p.Arg110Gln Uncertain significance ★ ⚠ same type
EFCAB14 p.Arg33Leu Uncertain significance ★ ⚠ same type
EFCAB14 p.Arg388Ser Uncertain significance ★ ⚠ same type
EFCAB14 p.Asn127Lys 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/efcab14-p-ser429phe (accessed [today's date]).

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