Is EVC2 p.Arg7Gln (c.20G>A) pathogenic?

EVC2 p.Arg7Gln (c.20G>A) is classified Uncertain significance in EVC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.2332); Very rare (popmax 0.00586%, afr); Associated with Inborn genetic diseases.

What condition is associated with EVC2 p.Arg7Gln (c.20G>A)?

EVC2 p.Arg7Gln (c.20G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EVC2 p.Arg7Gln (c.20G>A) in the general population?

EVC2 p.Arg7Gln (c.20G>A) is very rare (popmax 0.00586%, afr) (gnomAD).

What do computational predictors say about EVC2 p.Arg7Gln (c.20G>A)?

AlphaMissense predicts likely benign (score 0.2332) — an in-silico prediction, not a clinical call.

EVC2 p.Arg7Gln

c.20G>A · VCV3343561

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2332 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00586%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2332	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -2.2
Regional constraint	o/e 1.14	unconstrained · MANE · 146 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	6.209	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00586% African / African-American · 4/68,254 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00112%

Overall 0.000338% 5/1,479,636 alleles · very rare exomes 3/1,327,434 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00586%	17,064
South Asian	0.00129%	77,612

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: EVC2
Protein: p.Arg7Gln
Coding: c.20G>A
MANE Select: NM_147127
Type: single nucleotide variant
Location: chr4:5708494 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33

Full EVC2 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

EVC2 p.Arg7= Likely benign ★ same residue
EVC2 p.Gln1089Ter Pathogenic ★★ same condition
EVC2 p.Ala1132Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1150Asp Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1260Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala618Thr Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala703Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Arg1140Cys 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/evc2-p-arg7gln (accessed [today's date]).

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