Is EVC p.Leu27= (c.79C>T) pathogenic?

EVC p.Leu27= (c.79C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). Very rare (popmax 0.00229%, nfe); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Leu27= (c.79C>T)?

EVC p.Leu27= (c.79C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Leu27= (c.79C>T) in the general population?

EVC p.Leu27= (c.79C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

EVC p.Leu27=

c.79C>T · rs1723000600 · VCV1103981

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Conditions

Ellis-van Creveld syndrome

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 1	GERP 0.21, phastCons 0.43
Overall
CADD	7.488	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 20/872,444 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00122%

Overall 0.00201% 21/1,046,080 alleles · very rare exomes 20/898,530 · genomes 1/147,550 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,622
African / African-American	0.00172%	58,102

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.Leu27=
Coding: c.79C>T
MANE Select: NM_153717
dbSNP: rs1723000600
Type: single nucleotide variant
Location: chr4:5711459 (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

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

Also linked: acrofacial dysostosis, Weyers type

Similar variants

EVC p.Leu27_Ala31del Uncertain significance same residue
EVC p.Leu27_Ala31dup Uncertain significance same residue
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

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-leu27 (accessed [today's date]).

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