Is ECM1 p.Pro49= (c.147A>C) pathogenic?

ECM1 p.Pro49= (c.147A>C) is classified Likely benign in ECM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Rare (popmax 0.134%, afr).

How common is ECM1 p.Pro49= (c.147A>C) in the general population?

ECM1 p.Pro49= (c.147A>C) is rare (popmax 0.134%, afr) (gnomAD).

ECM1 p.Pro49=

c.147A>C · rs1364726581 · VCV789433

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.088	GERP -2, phastCons 0.02
Overall
CADD	6.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% African / African-American · 72/53,602 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.1%

Overall 0.0516% 537/1,040,818 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.392%	255
African / African-Americangrpmax	0.134%	744
Remaining individualsnot grpmax-eligible	0.0505%	1,979
Ashkenazi Jewishnot grpmax-eligible	0.0504%	1,985
European (non-Finnish)	0.0504%	1,985
East Asian	0.046%	2,172
Finnishnot grpmax-eligible	0.0449%	2,225
Admixed American	0.0438%	2,285
Middle Eastern	0.0232%	4,310
South Asian	0.0163%	6,134

Amish 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.Pro49=
Coding: c.147A>C
MANE Select: NM_004425
dbSNP: rs1364726581
Type: single nucleotide variant
Location: chr1:150509686 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 49: the 'disordered' region

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

Similar variants

ECM1 p.Pro49Gln Likely benign same residue
ECM1 p.Arg254Ter Pathogenic ★★ same type
ECM1 p.Arg416Ter Pathogenic/Likely pathogenic ★★ same type
ECM1 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same type
ECM1 p.Arg53Ter Pathogenic ★★ same type
ECM1 p.Cys269Tyr Pathogenic/Likely pathogenic ★★ same type
ECM1 c.122-3T>G Uncertain significance ★★ same type
ECM1 p.Arg185His 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/ecm1-p-pro49 (accessed [today's date]).

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