Is ELN p.Val136Ala (c.407T>C) pathogenic?

ELN p.Val136Ala (c.407T>C) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.3427); No allele count reported in gnomAD v4.1 (AN 1,607,936); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Val136Ala (c.407T>C)?

ELN p.Val136Ala (c.407T>C) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Val136Ala (c.407T>C) in the general population?

ELN p.Val136Ala (c.407T>C) is no allele count reported in gnomAD v4.1 (AN 1,607,936) (gnomAD).

What do computational predictors say about ELN p.Val136Ala (c.407T>C)?

AlphaMissense predicts ambiguous (score 0.3427) — an in-silico prediction, not a clinical call.

ELN p.Val136Ala

c.407T>C · VCV4738307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3427 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,936)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.3427	ambiguous
REVEL	0.123	moderately benign-leaning
SaProt	LLR -8.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -13, phastCons 0.45
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	0.151	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

No allele count reported in gnomAD v4.1 (AN 1,607,936). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELN
Protein: p.Val136Ala
Coding: c.407T>C
MANE Select: NM_000501
Type: single nucleotide variant
Location: chr7:74043148 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20

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

Disease context

supravalvular aortic stenosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELN p.Val136Met Uncertain significance ★★ ⚠ same residue
ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same condition
ELN c.643+1G>C Likely pathogenic ★★ same condition
ELN c.686-2A>G Likely pathogenic ★★ same condition
ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same condition
ELN c.800-2A>G Pathogenic ★★ same condition
ELN c.800-3C>G Pathogenic ★★ same condition
ELN c.82+1G>A Pathogenic/Likely pathogenic ★★ same condition

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/eln-p-val136ala (accessed [today's date]).

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