Is EFCAB13 p.Ser448Phe (c.1343C>T) pathogenic?

EFCAB13 p.Ser448Phe (c.1343C>T) is classified Uncertain significance in EFCAB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely benign (0.1472); Rare (popmax 0.11%, sas).

How common is EFCAB13 p.Ser448Phe (c.1343C>T) in the general population?

EFCAB13 p.Ser448Phe (c.1343C>T) is rare (popmax 0.11%, sas) (gnomAD).

What do computational predictors say about EFCAB13 p.Ser448Phe (c.1343C>T)?

AlphaMissense predicts likely benign (score 0.1472) — an in-silico prediction, not a clinical call.

EFCAB13 p.Ser448Phe

c.1343C>T · rs554788706 · VCV2592668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1472 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1472	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.18	phastCons 0.001
Regional constraint	o/e 0.86	unconstrained · MANE · 112 kb · p 6e-06 · regional, not allelic
Overall
CADD	6.302	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 0.11% South Asian · 93/84,894 alleles

Filtering AF 0.0915% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0848%

Overall 0.00947% 150/1,583,392 alleles · rare exomes 128/1,431,144 · genomes 22/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.11%	913
Middle Eastern	0.017%	5,874
Remaining individualsnot grpmax-eligible	0.0147%	6,784
East Asian	0.00448%	22,308
European (non-Finnish)	0.00367%	27,225
Admixed American	0.00195%	51,376
African / African-American	0.00137%	73,042

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: EFCAB13
Protein: p.Ser448Phe
Coding: c.1343C>T
MANE Select: NM_152347
dbSNP: rs554788706
Type: single nucleotide variant
Location: chr17:47374937 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 53.37
Residue 448: the 'disordered' region

Full EFCAB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB13 p.Ala453Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala605Gly Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala668Asp Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala680Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala750Ser Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg185Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg236Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg255Cys 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/efcab13-p-ser448phe (accessed [today's date]).

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