Is EVC p.Asp945fs (c.2829_2830del) pathogenic?

EVC p.Asp945fs (c.28292830del) is classified Conflicting classifications of pathogenicity in EVC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-22). Very rare (popmax 0.00333%, amr); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Asp945fs (c.2829_2830del)?

EVC p.Asp945fs (c.2829_2830del) is associated with Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Asp945fs (c.2829_2830del) in the general population?

EVC p.Asp945fs (c.2829_2830del) is very rare (popmax 0.00333%, amr) (gnomAD).

EVC p.Asp945fs

c.2829_2830del · rs1460851298 · VCV553456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Ellis-van Creveld syndrome

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 20 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.085	GERP -3.1, phastCons 0.012
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,976 alleles

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

Overall 0.00062% 10/1,613,820 alleles · very rare exomes 7/1,461,650 · genomes 3/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,988
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000593%	168,566

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.Asp945fs
Coding: c.2829_2830del
MANE Select: NM_153717
dbSNP: rs1460851298
Type: Microsatellite
Location: chr4:5810383 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 945: the 'disordered' region

Full EVC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ellis-van Creveld syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EVC p.Asp945= Likely benign ★ same residue
EVC p.Asp945Glu Uncertain significance ⚠ same residue
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.Phe583fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.39GL[4] Uncertain significance ★★ 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-asp945fs (accessed [today's date]).

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