Is ELN p.Ala441Val (c.1322C>T) pathogenic?

ELN p.Ala441Val (c.1322C>T) is classified Conflicting classifications of pathogenicity in ELN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-27). AlphaMissense: likely benign (0.3344); Ultra-rare (popmax 0.0624%, eas); Associated with Inborn genetic diseases.

What condition is associated with ELN p.Ala441Val (c.1322C>T)?

ELN p.Ala441Val (c.1322C>T) is associated with Inborn genetic diseases, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala441Val (c.1322C>T) in the general population?

ELN p.Ala441Val (c.1322C>T) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

What do computational predictors say about ELN p.Ala441Val (c.1322C>T)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

ELN p.Ala441Val

c.1322C>T · rs200444292 · VCV681179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -9.79	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 2.1	GERP 5.8, phastCons 0.91
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	19.04	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 0.0624% East Asian · 28/44,870 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00223% 36/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,602
Remaining individualsnot grpmax-eligible	0.0064%	15,625
African / African-American	0.00267%	37,521
South Asian	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,180,027

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: ELN
Protein: p.Ala441Val
Coding: c.1322C>T
MANE Select: NM_000501
dbSNP: rs200444292
Type: single nucleotide variant
Location: chr7:74056678 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: supravalvular aortic stenosis

Similar variants

ELN p.Ala441Thr 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-ala441val (accessed [today's date]).

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