Is EVC p.Phe534= (c.1602C>T) pathogenic?

EVC p.Phe534= (c.1602C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-20). Very rare (popmax 0.0022%, sas); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Phe534= (c.1602C>T)?

EVC p.Phe534= (c.1602C>T) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Phe534= (c.1602C>T) in the general population?

EVC p.Phe534= (c.1602C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

EVC p.Phe534=

c.1602C>T · rs766294209 · VCV757309

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -7.2	GERP -3.4
Overall
CADD	0.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,070 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000496% 8/1,614,142 alleles · very rare exomes 8/1,461,882 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,535
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,028
European (non-Finnish)	0.000339%	295,007

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.Phe534=
Coding: c.1602C>T
MANE Select: NM_153717
dbSNP: rs766294209
Type: single nucleotide variant
Location: chr4:5783590 (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-phe534 (accessed [today's date]).

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