Is VARS2 p.Arg202Pro (c.605G>C) pathogenic?

VARS2 p.Arg202Pro (c.605G>C) is classified Uncertain significance in VARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-01). AlphaMissense: ambiguous (0.4606); Very rare (popmax 0.00432%, nfe).

How common is VARS2 p.Arg202Pro (c.605G>C) in the general population?

VARS2 p.Arg202Pro (c.605G>C) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about VARS2 p.Arg202Pro (c.605G>C)?

AlphaMissense predicts ambiguous (score 0.4606) — an in-silico prediction, not a clinical call.

VARS2 p.Arg202Pro

c.605G>C · rs1242761387 · VCV1013497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4606	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -16.20	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -3.6
Overall
CADD	17.94	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 0.00432% European (non-Finnish) · 51/1,179,956 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00335% 54/1,614,032 alleles · very rare exomes 54/1,461,774 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,136
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	74,998

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: VARS2
Protein: p.Arg202Pro
Coding: c.605G>C
MANE Select: NM_020442
dbSNP: rs1242761387
Type: single nucleotide variant
Location: chr6:30916183 (GRCh38)
Structure: AlphaFold pLDDT 88.12
Residue 202: the gst c-terminal domain

Full VARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VARS2 p.Arg202Trp Uncertain significance ★ ⚠ same residue
VARS1 p.Arg1058Gln Likely pathogenic ★★ ⚠ same type
VARS1 p.Arg1119Cys Pathogenic/Likely pathogenic ★★ same type
VARS1 p.Arg1208Ter Pathogenic/Likely pathogenic ★★ same type
VARS1 p.Gln1039Ter Likely pathogenic ★★ same type
VARS1 p.Trp790Ter Pathogenic/Likely pathogenic ★★ same type
VARS2 c.1480-2A>G Likely pathogenic ★★ same type
VARS2 c.2467-2A>G Pathogenic/Likely pathogenic ★★ same type

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/vars2-p-arg202pro (accessed [today's date]).

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