Is EVC2 p.His780= (c.2340C>T) pathogenic?

EVC2 p.His780= (c.2340C>T) is classified Conflicting classifications of pathogenicity in EVC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-20). Ultra-rare (popmax 0.056%, sas); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC2 p.His780= (c.2340C>T)?

EVC2 p.His780= (c.2340C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC2 p.His780= (c.2340C>T) in the general population?

EVC2 p.His780= (c.2340C>T) is ultra-rare (popmax 0.056%, sas) (gnomAD).

EVC2 p.His780=

c.2340C>T · rs150691722 · VCV290666

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

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 -0.89	GERP -4.1
Overall
CADD	1.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% South Asian · 51/91,078 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00706% 114/1,614,030 alleles · ultra-rare exomes 91/1,461,878 · genomes 23/152,152 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Middle Eastern	0.0495%	2,020
African / African-American	0.0293%	3,409
Admixed American	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.0064%	15,627
East Asian	0.00446%	22,428
European (non-Finnish)	0.00186%	53,637

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: EVC2
Protein: p.His780=
Coding: c.2340C>T
MANE Select: NM_147127
dbSNP: rs150691722
Type: single nucleotide variant
Location: chr4:5622698 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33

Full EVC2 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

EVC2 c.2046+1G>A Likely pathogenic ★★ same condition
EVC2 c.2047-2A>G Likely pathogenic ★★ same condition
EVC2 c.229-1G>T Likely pathogenic ★★ same condition
EVC2 c.229-2A>G Likely pathogenic ★★ same condition
EVC2 c.3360+1G>A Pathogenic ★★ same condition
EVC2 c.3659+2T>C Pathogenic/Likely pathogenic ★★ same condition
EVC2 c.450+2T>C Likely pathogenic ★★ same condition
EVC2 c.451-2A>G 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/evc2-p-his780 (accessed [today's date]).

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