Is EVC p.Thr513= (c.1539C>T) pathogenic?

EVC p.Thr513= (c.1539C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Very rare (popmax 0.00334%, sas); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Thr513= (c.1539C>T)?

EVC p.Thr513= (c.1539C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Thr513= (c.1539C>T) in the general population?

EVC p.Thr513= (c.1539C>T) is very rare (popmax 0.00334%, sas) (gnomAD).

EVC p.Thr513=

c.1539C>T · rs549251750 · VCV1130138

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, sas)

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -3.5
Overall
CADD	0.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% South Asian · 3/89,924 alleles

Filtering AF 0.000886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000446%

Overall 0.00112% 18/1,611,360 alleles · very rare exomes 14/1,459,150 · genomes 4/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00334%	29,975
African / African-American	0.00267%	37,498
East Asian	0.00223%	44,820
European (non-Finnish)	0.00102%	98,263

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.Thr513=
Coding: c.1539C>T
MANE Select: NM_153717
dbSNP: rs549251750
Type: single nucleotide variant
Location: chr4:5756338 (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 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
EVC c.1886+5G>T Pathogenic/Likely pathogenic ★★ same condition
EVC c.2304+2T>C 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-thr513 (accessed [today's date]).

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