Is ECD p.Asn61Ser (c.182A>G) pathogenic?

ECD p.Asn61Ser (c.182A>G) is classified Uncertain significance in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.0763); Ultra-rare (popmax 0.0329%, sas).

How common is ECD p.Asn61Ser (c.182A>G) in the general population?

ECD p.Asn61Ser (c.182A>G) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

What do computational predictors say about ECD p.Asn61Ser (c.182A>G)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

ECD p.Asn61Ser

c.182A>G · VCV4015976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -2.00	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 7.9	GERP 2.2, phastCons 1
Overall
CADD	22.9	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 0.0329% South Asian · 30/91,088 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00212% 31/1,461,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Asn61Ser
Coding: c.182A>G
MANE Select: NM_006304 · reported on NM_007265
Type: single nucleotide variant
Location: chr10:73163756 (GRCh38)
Structure: AlphaFold pLDDT 69.87 · 140 PDB
Residue 61: an α-helix

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

Similar variants

SEM1 p.Glu61= Likely benign ★ same residue
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

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-asn61ser (accessed [today's date]).

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