Is ECM1 p.Asn124Ser (c.371A>G) pathogenic?

ECM1 p.Asn124Ser (c.371A>G) is classified Likely benign in ECM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.0597); Very rare (popmax 0.00636%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ECM1 p.Asn124Ser (c.371A>G)?

ECM1 p.Asn124Ser (c.371A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ECM1 p.Asn124Ser (c.371A>G) in the general population?

ECM1 p.Asn124Ser (c.371A>G) is very rare (popmax 0.00636%, nfe) (gnomAD).

What do computational predictors say about ECM1 p.Asn124Ser (c.371A>G)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

ECM1 p.Asn124Ser

c.371A>G · VCV3843325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -3.66	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 -0.98	GERP -2.5
Regional constraint	o/e 0.94	unconstrained · MANE · 5,254 bp · p 0.14 · regional, not allelic
Overall
CADD	0.033	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 0.00636% European (non-Finnish) · 75/1,179,904 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.0049% 79/1,613,804 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,732
Remaining individualsnot grpmax-eligible	0.0032%	31,234
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,988

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.Asn124Ser
Coding: c.371A>G
MANE Select: NM_004425
Type: single nucleotide variant
Location: chr1:150510168 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 124: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECM1 p.Asn124His Uncertain significance ★ ⚠ same residue
ECM1 p.Arg185His Uncertain significance ★★ ⚠ same condition
ECM1 p.Asn324His Uncertain significance ★★ ⚠ same condition
ECM1 p.Gln332Arg Uncertain significance ★★ ⚠ same condition
ECM1 p.Phe345Ile Uncertain significance ★★ ⚠ same condition
ECM1 p.Pro169Ala Uncertain significance ★★ ⚠ same condition
ECM1 p.Pro78Ser Uncertain significance ★★ ⚠ same condition
ECM1 p.Ser54Asn Uncertain significance ★★ ⚠ 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-asn124ser (accessed [today's date]).

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