Is ELN p.Ala608Val (c.1823C>T) pathogenic?

ELN p.Ala608Val (c.1823C>T) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely benign (0.1143); No allele count reported in gnomAD v4.1 (AN 1,609,732).

How common is ELN p.Ala608Val (c.1823C>T) in the general population?

ELN p.Ala608Val (c.1823C>T) is no allele count reported in gnomAD v4.1 (AN 1,609,732) (gnomAD).

What do computational predictors say about ELN p.Ala608Val (c.1823C>T)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

ELN p.Ala608Val

c.1823C>T · rs2132485409 · VCV1699704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,732)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.76	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 -2.2	GERP -11
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	7.46	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A670V vs ClinVar A608V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,732). 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.Ala608Val
Coding: c.1823C>T
MANE Select: NM_000501
dbSNP: rs2132485409
Type: single nucleotide variant
Location: chr7:74063189 (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

Similar variants

ELN c.134-1G>A Likely pathogenic ★★ same type
ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same type
ELN c.643+1G>A Pathogenic/Likely pathogenic ★★ same type
ELN c.643+1G>C Likely pathogenic ★★ same type
ELN c.686-2A>G Likely pathogenic ★★ same type
ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same type
ELN c.800-2A>G Pathogenic ★★ same type
ELN c.800-3C>G 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/eln-p-ala608val (accessed [today's date]).

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