Is EBF1 p.Ser451Pro (c.1351T>C) pathogenic?

EBF1 p.Ser451Pro (c.1351T>C) is classified Uncertain significance in EBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.0973); Ultra-rare (popmax 0.0179%, mid).

How common is EBF1 p.Ser451Pro (c.1351T>C) in the general population?

EBF1 p.Ser451Pro (c.1351T>C) is ultra-rare (popmax 0.0179%, mid) (gnomAD).

What do computational predictors say about EBF1 p.Ser451Pro (c.1351T>C)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

EBF1 p.Ser451Pro

c.1351T>C · rs1170847073 · VCV3086821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.41	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 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 14 kb · p 0.0071 · regional, not allelic
Overall
CADD	25.5	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 0.0179% Middle Eastern · 1/5,598 alleles

Filtering AF 8.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.7e-05%

Overall 0.000335% 5/1,494,390 alleles · ultra-rare exomes 4/1,342,258 · genomes 1/152,132 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0179%	5,598
European (non-Finnish)	0.00036%	278,071

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.Ser451Pro
Coding: c.1351T>C
MANE Select: NM_024007
dbSNP: rs1170847073
Type: single nucleotide variant
Location: chr5:158712988 (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.Ala39Pro Uncertain significance ★ ⚠ same type
EBF1 p.Ala423Ser Uncertain significance ★ ⚠ same type
EBF1 p.Ala423Val 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

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-ser451pro (accessed [today's date]).

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