Is EVC p.Asp590= (c.1770C>T) pathogenic?

EVC p.Asp590= (c.1770C>T) is classified Conflicting classifications of pathogenicity in EVC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.225%, afr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Asp590= (c.1770C>T)?

EVC p.Asp590= (c.1770C>T) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Asp590= (c.1770C>T) in the general population?

EVC p.Asp590= (c.1770C>T) is rare (popmax 0.225%, afr) (gnomAD).

EVC p.Asp590=

c.1770C>T · rs141755737 · VCV530946

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.225%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.4
Overall
CADD	0.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.225% African / African-American · 169/74,960 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.0128% 206/1,609,876 alleles · rare exomes 91/1,457,596 · genomes 115/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.225%	444
Middle Eastern	0.0331%	3,020
Admixed American	0.0304%	3,286
Remaining individualsnot grpmax-eligible	0.0225%	4,454
European (non-Finnish)	0.000255%	392,653

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.Asp590=
Coding: c.1770C>T
MANE Select: NM_153717
dbSNP: rs141755737
Type: single nucleotide variant
Location: chr4:5783758 (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

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

Also linked: Ellis-van Creveld syndrome

Similar variants

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
EVC c.2304+2T>C 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-asp590 (accessed [today's date]).

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