Is ECEL1 p.Gly679Ser (c.2035G>A) pathogenic?

ECEL1 p.Gly679Ser (c.2035G>A) is classified Uncertain significance in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-29). AlphaMissense: likely pathogenic (0.9301); Very rare (popmax 0.0047%, sas).

How common is ECEL1 p.Gly679Ser (c.2035G>A) in the general population?

ECEL1 p.Gly679Ser (c.2035G>A) is very rare (popmax 0.0047%, sas) (gnomAD).

What do computational predictors say about ECEL1 p.Gly679Ser (c.2035G>A)?

AlphaMissense predicts likely pathogenic (score 0.9301) — an in-silico prediction, not a clinical call.

ECEL1 p.Gly679Ser

c.2035G>A · rs150549103 · VCV1327709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0047%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9301	likely pathogenic
REVEL	0.965	strongly pathogenic-leaning
SaProt	LLR -12.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 6.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0047% South Asian · 4/85,024 alleles

Filtering AF 0.0016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00094%

Overall 0.00163% 23/1,413,264 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0047%	21,256
Remaining individualsnot grpmax-eligible	0.00165%	60,682
European (non-Finnish)	0.00156%	64,172

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.Gly679Ser
Coding: c.2035G>A
MANE Select: NM_004826
dbSNP: rs150549103
Type: single nucleotide variant
Location: chr2:232481111 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 679: a disulfide bond; the peptidase m13 domain

Full ECEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECEL1 c.1685+1G>A Pathogenic ★★ same type
ECEL1 c.2151+2T>C Likely pathogenic ★★ same type
ECEL1 c.966+1G>A Pathogenic ★★ same type
ECEL1 p.Ala675Thr Pathogenic ★★ same type
ECEL1 p.Arg333Ter Pathogenic ★★ same type
ECEL1 p.Arg395Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
ECEL1 p.Arg418Cys Likely pathogenic ★★ same type
ECEL1 p.Gln435Ter Pathogenic/Likely pathogenic ★★ 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/ecel1-p-gly679ser (accessed [today's date]).

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