Is EBP p.Ser65Phe (c.194C>T) pathogenic?

EBP p.Ser65Phe (c.194C>T) is classified Uncertain significance in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: likely benign (0.2741); Very rare (popmax 0.00351%, sas).

How common is EBP p.Ser65Phe (c.194C>T) in the general population?

EBP p.Ser65Phe (c.194C>T) is very rare (popmax 0.00351%, sas) (gnomAD).

What do computational predictors say about EBP p.Ser65Phe (c.194C>T)?

AlphaMissense predicts likely benign (score 0.2741) — an in-silico prediction, not a clinical call.

EBP p.Ser65Phe

c.194C>T · rs782294297 · VCV2991199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00351%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2741	likely benign
REVEL	0.611	indeterminate
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 2, phastCons 0.99
Overall
CADD	21.9	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 0.00351% South Asian · 2/56,983 alleles

Filtering AF 0.000582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000273% 3/1,098,236 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00351%	28,491
Remaining individualsnot grpmax-eligible	0.0021%	47,644

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: EBP
Protein: p.Ser65Phe
Coding: c.194C>T
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs782294297
Type: single nucleotide variant
Location: chrX:48523965 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 65: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

EBP p.Ser65Pro Uncertain significance ★ ⚠ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
EBP p.Arg110Ter Pathogenic ★★ same type
EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Arg147His Pathogenic ★★ ⚠ same type
EBP p.Arg62Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same type
EBP p.Gly161Arg Likely pathogenic ★★ 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/ebp-p-ser65phe (accessed [today's date]).

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