Is EFCAB11 p.Ser56Phe (c.167C>T) pathogenic?

EFCAB11 p.Ser56Phe (c.167C>T) is classified Uncertain significance in EFCAB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.9284); Very rare (popmax 0.00136%, nfe).

How common is EFCAB11 p.Ser56Phe (c.167C>T) in the general population?

EFCAB11 p.Ser56Phe (c.167C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about EFCAB11 p.Ser56Phe (c.167C>T)?

AlphaMissense predicts likely pathogenic (score 0.9284) — an in-silico prediction, not a clinical call.

EFCAB11 p.Ser56Phe

c.167C>T · VCV3843539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9284	likely pathogenic · top 9% in EFCAB11
REVEL	0.217	benign-leaning
SaProt	LLR -12.80	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.25, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 157 kb · p 0.87 · regional, not allelic
Overall
CADD	24.5	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 0.00136% European (non-Finnish) · 16/1,179,612 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,612,702 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,726
South Asian	0.0011%	90,952

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: EFCAB11
Protein: p.Ser56Phe
Coding: c.167C>T
MANE Select: NM_145231
Type: single nucleotide variant
Location: chr14:89953910 (GRCh38)
Gene constraint: LOEUF 1.06 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.38

Full EFCAB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB11 p.Ala15Asp Uncertain significance ★ ⚠ same type
EFCAB11 p.Ala163Val Uncertain significance ★ ⚠ same type
EFCAB11 p.Arg108Cys Uncertain significance ★ same type
EFCAB11 p.Arg108His Uncertain significance ★ ⚠ same type
EFCAB11 p.Arg141Gly Uncertain significance ★ ⚠ same type
EFCAB11 p.Arg7Thr Uncertain significance ★ ⚠ same type
EFCAB11 p.Arg93Gln Uncertain significance ★ ⚠ same type
EFCAB11 p.Asp140Asn 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/efcab11-p-ser56phe (accessed [today's date]).

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