Is EBF4 p.Ser473Arg (c.1419C>A) pathogenic?

EBF4 p.Ser473Arg (c.1419C>A) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.6648); Very rare (popmax 0.00977%, nfe).

How common is EBF4 p.Ser473Arg (c.1419C>A) in the general population?

EBF4 p.Ser473Arg (c.1419C>A) is very rare (popmax 0.00977%, nfe) (gnomAD).

What do computational predictors say about EBF4 p.Ser473Arg (c.1419C>A)?

AlphaMissense predicts likely pathogenic (score 0.6648) — an in-silico prediction, not a clinical call.

EBF4 p.Ser473Arg

c.1419C>A · rs1203275896 · VCV3086842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00977%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6648	likely pathogenic
REVEL	0.223	benign-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 9,329 bp · p 0.2 · regional, not allelic
Overall
CADD	23.5	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 0.00977% European (non-Finnish) · 100/1,023,244 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00826% 107/1,295,978 alleles · very rare exomes 105/1,144,422 · genomes 2/151,556 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0105%	9,543
European (non-Finnish)grpmax	0.00977%	10,232
African / African-American	0.00309%	32,323

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser473Arg
Coding: c.1419C>A
MANE Select: NM_001395167
dbSNP: rs1203275896
Type: single nucleotide variant
Location: chr20:2752424 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.60
Residue 473: the 'disordered' region

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-ser473arg (accessed [today's date]).

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