Is ECM2 p.Pro187His (c.560C>A) pathogenic?

ECM2 p.Pro187His (c.560C>A) is classified Uncertain significance in ECM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.0926); Very rare (popmax 0.000254%, nfe).

How common is ECM2 p.Pro187His (c.560C>A) in the general population?

ECM2 p.Pro187His (c.560C>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ECM2 p.Pro187His (c.560C>A)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

ECM2 p.Pro187His

c.560C>A · VCV3506524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP -0.32, phastCons 0.007
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.0043 · regional, not allelic
Overall
CADD	20.1	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 0.000254% European (non-Finnish) · 3/1,179,836 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,246 alleles · very rare exomes 3/1,461,044 · genomes 0/152,202 · joint denominator

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: ECM2
Protein: p.Pro187His
Coding: c.560C>A
MANE Select: NM_001393
Type: single nucleotide variant
Location: chr9:92515125 (GRCh38)

Full ECM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ecm2-p-pro187his (accessed [today's date]).

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