Is EVC p.Arg340Ter (c.1018C>T) pathogenic?

EVC p.Arg340Ter (c.1018C>T) is classified Pathogenic/Likely pathogenic in EVC (ClinVar, Multiple submitters, 14 submitters; last evaluated 2025-04-04). Very rare (popmax 0.00223%, eas); Associated with EVC-related disorder.

What condition is associated with EVC p.Arg340Ter (c.1018C>T)?

EVC p.Arg340Ter (c.1018C>T) is associated with EVC-related disorder, acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Arg340Ter (c.1018C>T) in the general population?

EVC p.Arg340Ter (c.1018C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

EVC p.Arg340Ter

c.1018C>T · rs121908425 · VCV5340

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

EVC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2, phastCons 1
Overall
CADD	41.0	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 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00173% 28/1,614,128 alleles · very rare exomes 23/1,461,890 · genomes 5/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
European (non-Finnish)	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,030

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.Arg340Ter
Coding: c.1018C>T
MANE Select: NM_153717
dbSNP: rs121908425
Type: single nucleotide variant
Location: chr4:5748226 (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

EVC-related disorder

Also linked: acrofacial dysostosis, Weyers type Ellis-van Creveld syndrome short-rib thoracic dysplasia 6 with or without polydactyly

Similar variants

EVC p.Arg340Gln Uncertain significance ★★ ⚠ same residue
EVC p.Arg340Pro Uncertain significance ★ ⚠ same residue
EVC p.Arg340= Likely benign ★ 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

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-arg340ter (accessed [today's date]).

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