Is ECM1 p.Asp367Val (c.1100A>T) pathogenic?

ECM1 p.Asp367Val (c.1100A>T) is classified Benign/Likely benign in ECM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.8177); Low-frequency (popmax 1.15%, nfe); Associated with lipoid proteinosis.

What condition is associated with ECM1 p.Asp367Val (c.1100A>T)?

ECM1 p.Asp367Val (c.1100A>T) is associated with lipoid proteinosis (ClinVar).

How common is ECM1 p.Asp367Val (c.1100A>T) in the general population?

ECM1 p.Asp367Val (c.1100A>T) is low-frequency (popmax 1.15%, nfe) (gnomAD).

What do computational predictors say about ECM1 p.Asp367Val (c.1100A>T)?

AlphaMissense predicts likely pathogenic (score 0.8177) — an in-silico prediction, not a clinical call.

ECM1 p.Asp367Val

c.1100A>T · rs151102225 · VCV376771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8177 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

lipoid proteinosis

Computational evidence

Protein change
AlphaMissense	0.8177	likely pathogenic
REVEL	0.581	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,254 bp · p 0.14 · regional, not allelic
Overall
CADD	24.8	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 1.15% European (non-Finnish) · 13,601/1,179,778 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.987% 15,923/1,612,804 alleles · low-frequency exomes 14,825/1,461,884 · genomes 1,098/150,920 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.6%	63
European (non-Finnish)grpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.891%	112
South Asian	0.593%	169
Finnishnot grpmax-eligible	0.579%	173
Admixed American	0.413%	242
African / African-American	0.176%	569
Middle Eastern	0.0825%	1,212

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ECM1
Protein: p.Asp367Val
Coding: c.1100A>T
MANE Select: NM_004425
dbSNP: rs151102225
Type: single nucleotide variant
Location: chr1:150512368 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 367: the '2 x approximate repeats' region

Full ECM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lipoid proteinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECM1 p.Arg254Ter Pathogenic ★★ same condition
ECM1 p.Arg416Ter Pathogenic/Likely pathogenic ★★ same condition
ECM1 p.Arg53Ter Pathogenic ★★ same condition
ECM1 p.Cys269Tyr Pathogenic/Likely pathogenic ★★ same condition
ECM1 c.122-3T>G Uncertain significance ★★ same condition
ECM1 p.Pro169Ala Uncertain significance ★★ same condition
ECM1 p.Ser250Leu Uncertain significance ★★ ⚠ same condition
ECM1 c.1083+10C>T Benign/Likely benign ★★ 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/ecm1-p-asp367val (accessed [today's date]).

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