Is EVC p.Phe473fs (c.1416del) pathogenic?

EVC p.Phe473fs (c.1416del) is classified Pathogenic in EVC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-07). Very rare (popmax 0.0011%, sas); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Phe473fs (c.1416del)?

EVC p.Phe473fs (c.1416del) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Phe473fs (c.1416del) in the general population?

EVC p.Phe473fs (c.1416del) is very rare (popmax 0.0011%, sas) (gnomAD).

EVC p.Phe473fs

c.1416del · rs768485560 · VCV618094

Pathogenic Multiple submitters

Classification

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 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -0.71

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 6.2e-05% 1/1,613,910 alleles · very rare exomes 1/1,461,560 · genomes 0/152,350 · joint denominator

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.Phe473fs
Coding: c.1416del
MANE Select: NM_153717
dbSNP: rs768485560
Type: Deletion
Location: chr4:5753885 (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.Phe473_Leu474insGlnArgSerPhe Uncertain significance ★ same residue
EVC c.1783_1886+40del Pathogenic ★★ same condition
EVC c.1887-5_1904del Pathogenic/Likely pathogenic ★★ same condition
EVC c.2782+1del Pathogenic ★★ same condition
EVC p.Ala565fs Pathogenic ★★ same condition
EVC p.Asn68fs Pathogenic ★★ same condition
EVC p.Asp132fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Gln424fs 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-phe473fs (accessed [today's date]).

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