Is ECM1 p.Pro78Ser (c.232C>T) pathogenic?

ECM1 p.Pro78Ser (c.232C>T) is classified Uncertain significance in ECM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-21). AlphaMissense: likely benign (0.0677); Very rare (popmax 0.00237%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ECM1 p.Pro78Ser (c.232C>T)?

ECM1 p.Pro78Ser (c.232C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ECM1 p.Pro78Ser (c.232C>T) in the general population?

ECM1 p.Pro78Ser (c.232C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about ECM1 p.Pro78Ser (c.232C>T)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

ECM1 p.Pro78Ser

c.232C>T · rs779818666 · VCV2479864

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Pangolin	Δ0.23	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.049	GERP 0.48
Regional constraint	o/e 0.94	unconstrained · MANE · 5,254 bp · p 0.14 · regional, not allelic
Overall
CADD	6.765	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 0.00237% European (non-Finnish) · 28/1,180,018 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00186% 30/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)grpmax	0.00237%	42,143

Remaining individuals 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.Pro78Ser
Coding: c.232C>T
MANE Select: NM_004425
dbSNP: rs779818666
Type: single nucleotide variant
Location: chr1:150509930 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 78: 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.Pro78fs Pathogenic/Likely pathogenic ★★ 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.Ser54Asn Uncertain significance ★★ ⚠ same condition
ECM1 c.223+68T>C 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-pro78ser (accessed [today's date]).

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