Is EVC p.Ser904= (c.2712C>T) pathogenic?

EVC p.Ser904= (c.2712C>T) is classified Conflicting classifications of pathogenicity in EVC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-15). Rare (popmax 0.118%, amr); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Ser904= (c.2712C>T)?

EVC p.Ser904= (c.2712C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Ser904= (c.2712C>T) in the general population?

EVC p.Ser904= (c.2712C>T) is rare (popmax 0.118%, amr) (gnomAD).

EVC p.Ser904=

c.2712C>T · rs146829332 · VCV386783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, amr)

Conditions

Ellis-van Creveld syndrome

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 -20	GERP -3
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% Admixed American · 71/60,006 alleles

Filtering AF 0.0962% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.088%

Overall 0.0105% 169/1,614,060 alleles · rare exomes 121/1,461,876 · genomes 48/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.118%	845
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.0147%	6,812
European (non-Finnish)	0.00585%	17,102
East Asian	0.00446%	22,443
South Asian	0.0011%	91,080

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: EVC
Protein: p.Ser904=
Coding: c.2712C>T
MANE Select: NM_153717
dbSNP: rs146829332
Type: single nucleotide variant
Location: chr4:5809541 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

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

Disease context

Ellis-van Creveld syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acrofacial dysostosis, Weyers type

Similar variants

EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1886+1G>C Likely pathogenic ★★ same condition
EVC c.1886+5G>A Pathogenic ★★ same condition
EVC c.1886+5G>T Pathogenic/Likely pathogenic ★★ same condition
EVC c.2304+2T>C 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/evc-p-ser904 (accessed [today's date]).

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