Is EVC p.Phe583fs (c.1746_1747del) pathogenic?

EVC p.Phe583fs (c.17461747del) is classified Pathogenic/Likely pathogenic in EVC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-10). Very rare (popmax 0.0011%, sas); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Phe583fs (c.1746_1747del)?

EVC p.Phe583fs (c.1746_1747del) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Phe583fs (c.1746_1747del) in the general population?

EVC p.Phe583fs (c.1746_1747del) is very rare (popmax 0.0011%, sas) (gnomAD).

EVC p.Phe583fs

c.1746_1747del · rs2152289369 · VCV1074980

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -3.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,006 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,592 alleles · very rare exomes 3/1,461,390 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,006
European (non-Finnish)	0.00017%	589,887

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.Phe583fs
Coding: c.1746_1747del
MANE Select: NM_153717
dbSNP: rs2152289369
Type: Microsatellite
Location: chr4:5783732 (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 p.Arg13fs Pathogenic ★★ same condition
EVC p.Cys554_Asp555delinsTer Pathogenic/Likely pathogenic ★★ same condition
EVC p.Leu346fs Pathogenic ★★ same condition
EVC p.Lys302del Pathogenic/Likely pathogenic ★★ same condition
EVC p.39GL[4] Uncertain significance ★★ same condition
EVC c.2895-10_2895-9del Benign/Likely benign ★★ same condition
EVC p.Arg471fs Pathogenic ★ same condition
EVC p.Asp290_Ser291insTer 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-phe583fs (accessed [today's date]).

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