Is EBPL p.Ala39Val (c.116C>T) pathogenic?

EBPL p.Ala39Val (c.116C>T) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1104); Ultra-rare (popmax 0.0306%, eas).

How common is EBPL p.Ala39Val (c.116C>T) in the general population?

EBPL p.Ala39Val (c.116C>T) is ultra-rare (popmax 0.0306%, eas) (gnomAD).

What do computational predictors say about EBPL p.Ala39Val (c.116C>T)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

EBPL p.Ala39Val

c.116C>T · VCV4246298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -3.75	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 3.6	GERP 0.61, phastCons 0.86
Regional constraint	o/e 1.02	unconstrained · MANE · 28 kb · p 0.82 · regional, not allelic
Overall
CADD	15.02	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 0.0306% East Asian · 10/32,678 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0126%

Overall 0.00125% 17/1,364,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0306%	3,268
Remaining individualsnot grpmax-eligible	0.00588%	17,001
Ashkenazi Jewishnot grpmax-eligible	0.00455%	21,964
South Asian	0.00193%	51,930
European (non-Finnish)	0.00019%	527,426

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: EBPL
Protein: p.Ala39Val
Coding: c.116C>T
MANE Select: NM_032565
Type: single nucleotide variant
Location: chr13:49691309 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 39: the expera domain

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

Similar variants

EBPL p.Ala107Ser Uncertain significance ★ ⚠ same type
EBPL p.Ala107Thr Uncertain significance ★ ⚠ same type
EBPL p.Ala11Gly Uncertain significance ★ ⚠ same type
EBPL p.Ala23Glu Uncertain significance ★ ⚠ same type
EBPL p.Ala27Thr Uncertain significance ★ ⚠ same type
EBPL p.Ala38Val Uncertain significance ★ ⚠ same type
EBPL p.Ala43Gly Uncertain significance ★ ⚠ same type
EBPL p.Ala89Val 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/ebpl-p-ala39val (accessed [today's date]).

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