Is EBF4 p.Val48Met (c.142G>A) pathogenic?

EBF4 p.Val48Met (c.142G>A) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.2688); Very rare (popmax 0.00733%, eas).

How common is EBF4 p.Val48Met (c.142G>A) in the general population?

EBF4 p.Val48Met (c.142G>A) is very rare (popmax 0.00733%, eas) (gnomAD).

What do computational predictors say about EBF4 p.Val48Met (c.142G>A)?

AlphaMissense predicts likely benign (score 0.2688) — an in-silico prediction, not a clinical call.

EBF4 p.Val48Met

c.142G>A · rs749337026 · VCV2349935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00733%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2688	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -10.59	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	31.0	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 0.00733% East Asian · 3/40,936 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00187% 29/1,551,850 alleles · very rare exomes 27/1,399,586 · genomes 2/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00733%	13,645
South Asian	0.00476%	21,017
Remaining individualsnot grpmax-eligible	0.00333%	30,065
African / African-American	0.00273%	36,580
European (non-Finnish)	0.00157%	63,726

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: EBF4
Protein: p.Val48Met
Coding: c.142G>A
MANE Select: NM_001395167
dbSNP: rs749337026
Type: single nucleotide variant
Location: chr20:2705581 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.60

Full EBF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF4 p.Arg164= Benign ★★ same type
EBF4 p.Ile91= Benign ★★ same type
EBF4 p.Ala102Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala102Val Uncertain significance ★ ⚠ same type
EBF4 p.Ala402Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala40Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala438Ser Uncertain significance ★ ⚠ same type
EBF4 p.Ala522Val 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/ebf4-p-val48met (accessed [today's date]).

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