Is EVC2 p.Lys1279= (c.3837G>A) pathogenic?

EVC2 p.Lys1279= (c.3837G>A) is classified Conflicting classifications of pathogenicity in EVC2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Rare (popmax 0.264%, mid); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC2 p.Lys1279= (c.3837G>A)?

EVC2 p.Lys1279= (c.3837G>A) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC2 p.Lys1279= (c.3837G>A) in the general population?

EVC2 p.Lys1279= (c.3837G>A) is rare (popmax 0.264%, mid) (gnomAD).

EVC2 p.Lys1279=

c.3837G>A · rs201651890 · VCV262616

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.264%, mid)

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 2	GERP 0.82, phastCons 0.97
Overall
CADD	4.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% Middle Eastern · 16/6,062 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0044% 71/1,614,072 alleles · rare exomes 60/1,461,884 · genomes 11/152,188 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.264%	379
African / African-American	0.0467%	2,143
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.000763%	131,113

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.Lys1279=
Coding: c.3837G>A
MANE Select: NM_147127
dbSNP: rs201651890
Type: single nucleotide variant
Location: chr4:5562938 (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 p.Lys1279Glu Uncertain significance ★ ⚠ same residue
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

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-lys1279 (accessed [today's date]).

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