Is EVC p.Arg18Trp (c.52C>T) pathogenic?

EVC p.Arg18Trp (c.52C>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: ambiguous (0.4567); No allele count reported in gnomAD v4.1 (AN 1,024,446); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Arg18Trp (c.52C>T)?

EVC p.Arg18Trp (c.52C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Arg18Trp (c.52C>T) in the general population?

EVC p.Arg18Trp (c.52C>T) is no allele count reported in gnomAD v4.1 (AN 1,024,446) (gnomAD).

What do computational predictors say about EVC p.Arg18Trp (c.52C>T)?

AlphaMissense predicts ambiguous (score 0.4567) — an in-silico prediction, not a clinical call.

EVC p.Arg18Trp

c.52C>T · VCV3846585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4567 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,024,446)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4567	ambiguous
REVEL	0.191	benign-leaning
SaProt	LLR -7.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.85	GERP -0.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	24.2	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

No allele count reported in gnomAD v4.1 (AN 1,024,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EVC
Protein: p.Arg18Trp
Coding: c.52C>T
MANE Select: NM_153717
Type: single nucleotide variant
Location: chr4:5711432 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EVC p.Arg18Leu Uncertain significance ★★ ⚠ same residue
EVC p.Arg18= Likely benign ★ same residue
EVC p.Ala20Pro Uncertain significance ★★ ⚠ same condition
EVC p.Ala365Asp Uncertain significance ★★ ⚠ same condition
EVC p.Ala365Thr Uncertain significance ★★ ⚠ same condition
EVC p.Arg340Gln Uncertain significance ★★ ⚠ same condition
EVC p.Arg438Trp Uncertain significance ★★ ⚠ same condition
EVC p.Arg622Gln Uncertain significance ★★ ⚠ 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-arg18trp (accessed [today's date]).

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