Is VARS2 p.Val312= (c.936G>A) pathogenic?

VARS2 p.Val312= (c.936G>A) is classified Likely benign in VARS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-20). Ultra-rare (popmax 0.0257%, afr); Associated with VARS2-related disorder.

What condition is associated with VARS2 p.Val312= (c.936G>A)?

VARS2 p.Val312= (c.936G>A) is associated with VARS2-related disorder (ClinVar).

How common is VARS2 p.Val312= (c.936G>A) in the general population?

VARS2 p.Val312= (c.936G>A) is ultra-rare (popmax 0.0257%, afr) (gnomAD).

VARS2 p.Val312=

c.936G>A · rs200908750 · VCV3053217

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0257%, afr)

Conditions

VARS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.7, phastCons 1
Overall
CADD	9.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0257% African / African-American · 19/73,890 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.00147% 23/1,566,390 alleles · ultra-rare exomes 11/1,414,178 · genomes 12/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0257%	3,889
Admixed American	0.00566%	17,675
Remaining individualsnot grpmax-eligible	0.00165%	60,688

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.Val312=
Coding: c.936G>A
MANE Select: NM_020442
dbSNP: rs200908750
Type: single nucleotide variant
Location: chr6:30917757 (GRCh38)
Structure: AlphaFold pLDDT 88.12

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

Disease context

VARS2-related disorder

Similar variants

VARS2 p.Val312Met Uncertain significance ★★ ⚠ same residue
VARS2 p.Val495Gly Uncertain significance ★★ ⚠ same condition
VARS1 p.Gln126Ter Likely pathogenic ★ same condition
VARS2 p.Arg171Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
VARS2 p.Arg439Trp Uncertain significance ★ same condition
VARS2 p.Arg490Ter Conflicting classifications of pathogenicity ★ same condition
VARS1 p.Ala74= Likely benign same condition
VARS1 p.Arg1217Cys Benign ⚠ 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/vars2-p-val312 (accessed [today's date]).

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