Is EVC2 p.Lys1187= (c.3561A>G) pathogenic?

EVC2 p.Lys1187= (c.3561A>G) is classified Benign/Likely benign in EVC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.25%, afr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC2 p.Lys1187= (c.3561A>G)?

EVC2 p.Lys1187= (c.3561A>G) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC2 p.Lys1187= (c.3561A>G) in the general population?

EVC2 p.Lys1187= (c.3561A>G) is low-frequency (popmax 1.25%, afr) (gnomAD).

EVC2 p.Lys1187=

c.3561A>G · rs76523157 · VCV506668

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, afr)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.7	GERP -3.5
Overall
CADD	3.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% African / African-American · 940/74,990 alleles

Filtering AF 1.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.16%

Overall 0.066% 1,066/1,613,986 alleles · low-frequency exomes 517/1,461,746 · genomes 549/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.25%	80
Admixed American	0.0916%	1,091
Remaining individualsnot grpmax-eligible	0.0896%	1,116
Middle Eastern	0.066%	1,514
South Asian	0.00439%	22,769
European (non-Finnish)	0.000593%	168,562

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.Lys1187=
Coding: c.3561A>G
MANE Select: NM_147127
dbSNP: rs76523157
Type: single nucleotide variant
Location: chr4:5565356 (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

acrofacial dysostosis, Weyers type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ellis-van Creveld syndrome

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-lys1187 (accessed [today's date]).

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