Is ECD p.Asp504Ala (c.1511A>C) pathogenic?

ECD p.Asp504Ala (c.1511A>C) is classified Uncertain significance in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-30). AlphaMissense: likely benign (0.1618); Rare (popmax 0.114%, nfe).

How common is ECD p.Asp504Ala (c.1511A>C) in the general population?

ECD p.Asp504Ala (c.1511A>C) is rare (popmax 0.114%, nfe) (gnomAD).

What do computational predictors say about ECD p.Asp504Ala (c.1511A>C)?

AlphaMissense predicts likely benign (score 0.1618) — an in-silico prediction, not a clinical call.

ECD p.Asp504Ala

c.1511A>C · rs147899211 · VCV2401833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1618 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1618	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -8.27	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 6	GERP 0.68, phastCons 1
Overall
CADD	24.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% European (non-Finnish) · 1,345/1,179,918 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0923% 1,490/1,613,674 alleles · rare exomes 1,414/1,461,558 · genomes 76/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.114%	877
Remaining individualsnot grpmax-eligible	0.0752%	1,329
South Asian	0.0703%	1,423
Middle Eastern	0.0338%	2,960
Finnishnot grpmax-eligible	0.0203%	4,916
Admixed American	0.015%	6,668
African / African-American	0.012%	8,335
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592

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.Asp504Ala
Coding: c.1511A>C
MANE Select: NM_007265
dbSNP: rs147899211
Type: single nucleotide variant
Location: chr10:73136897 (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-asp504ala (accessed [today's date]).

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