Is EBPL p.Val136Met (c.406G>A) pathogenic?

EBPL p.Val136Met (c.406G>A) is classified Uncertain significance in EBPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.1789); Very rare (popmax 0.0033%, sas).

How common is EBPL p.Val136Met (c.406G>A) in the general population?

EBPL p.Val136Met (c.406G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about EBPL p.Val136Met (c.406G>A)?

AlphaMissense predicts likely benign (score 0.1789) — an in-silico prediction, not a clinical call.

EBPL p.Val136Met

c.406G>A · VCV3274373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1789	likely benign
REVEL	0.709	pathogenic-leaning
SaProt	LLR -9.88	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.17, phastCons 0.99
Regional constraint	o/e 0.52	unconstrained · MANE · 2,093 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	22.0	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 0.0033% South Asian · 3/91,020 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00093% 15/1,613,742 alleles · very rare exomes 12/1,461,600 · genomes 3/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,340
African / African-American	0.00267%	37,443
Admixed American	0.00167%	59,922
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00156%	64,014
European (non-Finnish)	0.000593%	168,564

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.Val136Met
Coding: c.406G>A
MANE Select: NM_032565
Type: single nucleotide variant
Location: chr13:49661183 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06
Residue 136: 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.Ala39Val Uncertain significance ★ ⚠ same type
EBPL p.Ala43Gly 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-val136met (accessed [today's date]).

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