Is EVC p.Asp208= (c.624C>T) pathogenic?

EVC p.Asp208= (c.624C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-29). Very rare (popmax 0.00333%, amr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Asp208= (c.624C>T)?

EVC p.Asp208= (c.624C>T) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Asp208= (c.624C>T) in the general population?

EVC p.Asp208= (c.624C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

EVC p.Asp208=

c.624C>T · rs187457187 · VCV1595541

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP 0.63, phastCons 1
Overall
CADD	10.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,030 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,528 alleles · very rare exomes 6/1,461,266 · genomes 1/152,262 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,015
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	75,008
South Asian	0.0011%	91,070
European (non-Finnish)	8.48e-05%	1,179,526

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.Asp208=
Coding: c.624C>T
MANE Select: NM_153717
dbSNP: rs187457187
Type: single nucleotide variant
Location: chr4:5733357 (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-asp208 (accessed [today's date]).

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