Is EBF1 p.Ala423Val (c.1268C>T) pathogenic?

EBF1 p.Ala423Val (c.1268C>T) is classified Uncertain significance in EBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0202%, afr).

How common is EBF1 p.Ala423Val (c.1268C>T) in the general population?

EBF1 p.Ala423Val (c.1268C>T) is ultra-rare (popmax 0.0202%, afr) (gnomAD).

What do computational predictors say about EBF1 p.Ala423Val (c.1268C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

EBF1 p.Ala423Val

c.1268C>T · VCV4015908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 14 kb · p 0.0071 · regional, not allelic
Overall
CADD	25.7	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 0.0202% African / African-American · 15/74,276 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00997%

Overall 0.00106% 17/1,597,824 alleles · ultra-rare exomes 9/1,445,680 · genomes 8/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0202%	4,952
Remaining individualsnot grpmax-eligible	0.00162%	61,710
European (non-Finnish)	8.54e-05%	1,171,047

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: EBF1
Protein: p.Ala423Val
Coding: c.1268C>T
MANE Select: NM_024007
Type: single nucleotide variant
Location: chr5:158713071 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.07 · 2 PDB

Full EBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF1 p.Ala423Ser Uncertain significance ★ ⚠ same residue
EBF1 p.Ala39Pro Uncertain significance ★ ⚠ same type
EBF1 p.Ala425Val Uncertain significance ★ ⚠ same type
EBF1 p.Ala431Thr Uncertain significance ★ ⚠ same type
EBF1 p.Ala43Val Uncertain significance ★ ⚠ same type
EBF1 p.Ala510Gly Uncertain significance ★ ⚠ same type
EBF1 p.Ala516Thr Uncertain significance ★ ⚠ same type
EBF1 p.Ala582Glu 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/ebf1-p-ala423val (accessed [today's date]).

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