Is EVC p.Arg702Cys (c.2104C>T) pathogenic?

EVC p.Arg702Cys (c.2104C>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.244); Very rare (popmax 0.00588%, sas); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Arg702Cys (c.2104C>T)?

EVC p.Arg702Cys (c.2104C>T) is associated with Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Arg702Cys (c.2104C>T) in the general population?

EVC p.Arg702Cys (c.2104C>T) is very rare (popmax 0.00588%, sas) (gnomAD).

What do computational predictors say about EVC p.Arg702Cys (c.2104C>T)?

AlphaMissense predicts likely benign (score 0.244) — an in-silico prediction, not a clinical call.

EVC p.Arg702Cys

c.2104C>T · rs545087909 · VCV349194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
AlphaMissense	0.244	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00588% South Asian · 5/85,014 alleles

Filtering AF 0.00222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.000767% 12/1,565,322 alleles · very rare exomes 12/1,412,954 · genomes 0/152,368 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00588%	17,003
Admixed American	0.00189%	52,900
Remaining individualsnot grpmax-eligible	0.00165%	60,568
European (non-Finnish)	0.000432%	231,214

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.Arg702Cys
Coding: c.2104C>T
MANE Select: NM_153717
dbSNP: rs545087909
Type: single nucleotide variant
Location: chr4:5798592 (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

Similar variants

EVC p.Arg702Gly Uncertain significance ★★ ⚠ same residue
EVC p.Arg702His 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-arg702cys (accessed [today's date]).

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