Is ECEL1 p.Pro34Ser (c.100C>T) pathogenic?

ECEL1 p.Pro34Ser (c.100C>T) is classified Uncertain significance in ECEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0791); Ultra-rare (popmax 0.0701%, afr); Associated with Inborn genetic diseases.

What condition is associated with ECEL1 p.Pro34Ser (c.100C>T)?

ECEL1 p.Pro34Ser (c.100C>T) is associated with Inborn genetic diseases, distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Pro34Ser (c.100C>T) in the general population?

ECEL1 p.Pro34Ser (c.100C>T) is ultra-rare (popmax 0.0701%, afr) (gnomAD).

What do computational predictors say about ECEL1 p.Pro34Ser (c.100C>T)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

ECEL1 p.Pro34Ser

c.100C>T · rs955251142 · VCV1333926

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0701%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.6	GERP 0.99, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	18.17	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 0.0701% African / African-American · 46/65,622 alleles

Filtering AF 0.0539% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0482%

Overall 0.00381% 52/1,363,444 alleles · ultra-rare exomes 23/1,211,688 · genomes 29/151,756 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0701%	1,427
Admixed American	0.0105%	9,567
Finnishnot grpmax-eligible	0.00254%	39,302
European (non-Finnish)	0.000188%	531,932

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: ECEL1
Protein: p.Pro34Ser
Coding: c.100C>T
MANE Select: NM_004826
dbSNP: rs955251142
Type: single nucleotide variant
Location: chr2:232486554 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62

Full ECEL1 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

Also linked: distal arthrogryposis type 5D

Similar variants

ECEL1 p.Pro34Arg Uncertain significance ★ ⚠ same residue
ECEL1 p.Pro34Thr Uncertain significance ★ ⚠ same residue
ECEL1 c.1685+1G>A Pathogenic ★★ same condition
ECEL1 c.2151+2T>C Likely pathogenic ★★ same condition
ECEL1 c.966+1G>A Pathogenic ★★ same condition
ECEL1 p.Ala675Thr Pathogenic ★★ same condition
ECEL1 p.Arg333Ter Pathogenic ★★ same condition
ECEL1 p.Arg395Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/ecel1-p-pro34ser (accessed [today's date]).

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