Is EVC p.Arg935= (c.2805G>A) pathogenic?

EVC p.Arg935= (c.2805G>A) is classified Conflicting classifications of pathogenicity in EVC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-13). Rare (popmax 0.115%, afr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Arg935= (c.2805G>A)?

EVC p.Arg935= (c.2805G>A) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Arg935= (c.2805G>A) in the general population?

EVC p.Arg935= (c.2805G>A) is rare (popmax 0.115%, afr) (gnomAD).

EVC p.Arg935=

c.2805G>A · rs143631233 · VCV733306

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, 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	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.92	GERP -0.5, phastCons 1
Overall
CADD	3.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% African / African-American · 86/75,052 alleles

Filtering AF 0.095% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.00638% 103/1,613,806 alleles · rare exomes 54/1,461,514 · genomes 49/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.115%	873
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00334%	29,984
European (non-Finnish)	0.000593%	168,561

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.Arg935=
Coding: c.2805G>A
MANE Select: NM_153717
dbSNP: rs143631233
Type: single nucleotide variant
Location: chr4:5810361 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 935: the 'disordered' region

Full EVC 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

EVC p.Arg935fs Likely pathogenic ★ 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
EVC c.1886+5G>T 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-arg935 (accessed [today's date]).

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