Is ECD p.Val596Ala (c.1787T>C) pathogenic?

ECD p.Val596Ala (c.1787T>C) is classified Uncertain significance in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.3014); Very rare (popmax 0.000169%, nfe).

How common is ECD p.Val596Ala (c.1787T>C) in the general population?

ECD p.Val596Ala (c.1787T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ECD p.Val596Ala (c.1787T>C)?

AlphaMissense predicts likely benign (score 0.3014) — an in-silico prediction, not a clinical call.

ECD p.Val596Ala

c.1787T>C · rs1257240907 · VCV2550192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3014 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3014	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Overall
CADD	26.3	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 0.000169% European (non-Finnish) · 2/1,180,046 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,218 alleles · very rare

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: ECD
Protein: p.Val596Ala
Coding: c.1787T>C
MANE Select: NM_006304 · reported on NM_007265
dbSNP: rs1257240907
Type: single nucleotide variant
Location: chr10:73134731 (GRCh38)
Structure: AlphaFold pLDDT 69.87 · 140 PDB

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

Similar variants

ECD p.Ala121Gly Uncertain significance ★ ⚠ same type
ECD p.Ala122Ser Uncertain significance ★ ⚠ same type
ECD p.Ala150Thr Uncertain significance ★ ⚠ same type
ECD p.Ala234Ser Uncertain significance ★ ⚠ same type
ECD p.Ala329Val Uncertain significance ★ ⚠ same type
ECD p.Arg188Leu Uncertain significance ★ ⚠ same type
ECD p.Arg244Gln Uncertain significance ★ ⚠ same type
ECD p.Arg281Gln 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/ecd-p-val596ala (accessed [today's date]).

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