Is EVC p.Gly618= (c.1854C>T) pathogenic?

EVC p.Gly618= (c.1854C>T) is classified Benign in EVC (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-05-08). Common (popmax 52.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Gly618= (c.1854C>T)?

EVC p.Gly618= (c.1854C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

EVC p.Gly618=

Q: How common is EVC p.Gly618= (c.1854C>T) in the general population?

EVC p.Gly618= (c.1854C>T) is common (popmax 52.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1854C>T · rs11737221 · VCV262769

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 52.1%, sas) — too common for a highly-penetrant pathogenic allele

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 -1.5	GERP -4
Overall
CADD	1.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.1% South Asian · 43,794/84,018 alleles

Filtering AF 51.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.5%

Overall 32.7% 506,963/1,550,636 alleles · common exomes 465,360/1,398,626 · genomes 41,603/152,010 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	52.1%	2
East Asian	50.6%	2
Amishnot grpmax-eligible	35%	3
Admixed American	33.4%	3
Middle Eastern	33%	3
Remaining individualsnot grpmax-eligible	32.9%	3
European (non-Finnish)	32.1%	3
Finnishnot grpmax-eligible	31.9%	3
Ashkenazi Jewishnot grpmax-eligible	30.5%	3
African / African-American	10.1%	10

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.Gly618=
Coding: c.1854C>T
MANE Select: NM_153717
dbSNP: rs11737221
Type: single nucleotide variant
Location: chr4:5793685 (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.Gly618Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
EVC p.Gly618Asp 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-gly618 (accessed [today's date]).

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