Is EFCAB9 p.Leu48Val (c.142C>G) pathogenic?

EFCAB9 p.Leu48Val (c.142C>G) is classified Uncertain significance in EFCAB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1029); Very rare (popmax 0.00196%, amr).

How common is EFCAB9 p.Leu48Val (c.142C>G) in the general population?

EFCAB9 p.Leu48Val (c.142C>G) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about EFCAB9 p.Leu48Val (c.142C>G)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

EFCAB9 p.Leu48Val

c.142C>G · VCV4247023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.75	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 0.66	GERP -0.51, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 9,169 bp · p 0.074 · regional, not allelic
Overall
CADD	15.47	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 0.00196% Admixed American · 1/50,970 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00026% 4/1,537,092 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00196%	50,970
European (non-Finnish)	0.000262%	382,301

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: EFCAB9
Protein: p.Leu48Val
Coding: c.142C>G
MANE Select: NM_001171183
Type: single nucleotide variant
Location: chr5:172199388 (GRCh38)
Gene constraint: LOEUF 1.493 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00

Full EFCAB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB9 p.Ala75Pro Uncertain significance ★ ⚠ same type
EFCAB9 p.Arg105Gly Uncertain significance ★ ⚠ same type
EFCAB9 p.Arg105His Uncertain significance ★ ⚠ same type
EFCAB9 p.Arg108Gln Uncertain significance ★ ⚠ same type
EFCAB9 p.Arg146Cys Uncertain significance ★ ⚠ same type
EFCAB9 p.Arg155Cys Uncertain significance ★ ⚠ same type
EFCAB9 p.Asn135Ser Uncertain significance ★ ⚠ same type
EFCAB9 p.Asp115Tyr 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/efcab9-p-leu48val (accessed [today's date]).

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