Is EVC p.Asn196= (c.588C>T) pathogenic?

EVC p.Asn196= (c.588C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). Ultra-rare (popmax 0.0245%, eas); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Asn196= (c.588C>T)?

EVC p.Asn196= (c.588C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Asn196= (c.588C>T) in the general population?

EVC p.Asn196= (c.588C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

EVC p.Asn196=

c.588C>T · rs756994584 · VCV1146887

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

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 0.53	GERP -0.44, phastCons 0.07
Overall
CADD	9.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,880 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00192% 31/1,614,040 alleles · ultra-rare exomes 22/1,461,874 · genomes 9/152,166 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
African / African-American	0.00801%	12,488
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,541
European (non-Finnish)	0.000847%	118,003

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.Asn196=
Coding: c.588C>T
MANE Select: NM_153717
dbSNP: rs756994584
Type: single nucleotide variant
Location: chr4:5731628 (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.Asn196Ser Uncertain significance ★ ⚠ same residue
EVC p.Asn196Ter Likely pathogenic ★ 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-asn196 (accessed [today's date]).

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