Is VARS2 p.Ala489Asp (c.1466C>A) pathogenic?

VARS2 p.Ala489Asp (c.1466C>A) is classified Uncertain significance in VARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-07). AlphaMissense: likely benign (0.0575); No allele count reported in gnomAD v4.1 (AN 1,596,124).

How common is VARS2 p.Ala489Asp (c.1466C>A) in the general population?

VARS2 p.Ala489Asp (c.1466C>A) is no allele count reported in gnomAD v4.1 (AN 1,596,124) (gnomAD).

What do computational predictors say about VARS2 p.Ala489Asp (c.1466C>A)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

VARS2 p.Ala489Asp

c.1466C>A · rs1258779173 · VCV2096888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,124)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -4.2
Overall
CADD	1.534	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

No allele count reported in gnomAD v4.1 (AN 1,596,124). 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: VARS2
Protein: p.Ala489Asp
Coding: c.1466C>A
MANE Select: NM_020442
dbSNP: rs1258779173
Type: single nucleotide variant
Location: chr6:30920736 (GRCh38)
Structure: AlphaFold pLDDT 88.12

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

Similar variants

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
VARS2 p.Arg1002Ter 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-ala489asp (accessed [today's date]).

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