Is EVC p.Tyr780= (c.2340C>T) pathogenic?

EVC p.Tyr780= (c.2340C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Ultra-rare (popmax 0.0167%, amr); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Tyr780= (c.2340C>T)?

EVC p.Tyr780= (c.2340C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Tyr780= (c.2340C>T) in the general population?

EVC p.Tyr780= (c.2340C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

EVC p.Tyr780=

c.2340C>T · rs747263163 · VCV1978631

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, 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 -7	GERP -3.2
Overall
CADD	1.747	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,008 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00204% 33/1,613,930 alleles · ultra-rare exomes 30/1,461,712 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
East Asian	0.00668%	14,959
European (non-Finnish)	0.00161%	62,107
African / African-American	0.00133%	74,936

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.Tyr780=
Coding: c.2340C>T
MANE Select: NM_153717
dbSNP: rs747263163
Type: single nucleotide variant
Location: chr4:5801985 (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 p.Tyr780Cys Uncertain significance ★ same residue
EVC p.Tyr780Ser Uncertain significance ★ same residue
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

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-tyr780 (accessed [today's date]).

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