Is APRT p.Gly44Val (c.131G>T) pathogenic?

APRT p.Gly44Val (c.131G>T) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1626); Very rare (popmax 0.00936%, afr); Associated with Inborn genetic diseases.

What condition is associated with APRT p.Gly44Val (c.131G>T)?

APRT p.Gly44Val (c.131G>T) is associated with Inborn genetic diseases (ClinVar).

How common is APRT p.Gly44Val (c.131G>T) in the general population?

APRT p.Gly44Val (c.131G>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about APRT p.Gly44Val (c.131G>T)?

AlphaMissense predicts likely benign (score 0.1626) — an in-silico prediction, not a clinical call.

APRT p.Gly44Val

c.131G>T · VCV4128274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1626	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -1.4, phastCons 0.001
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	15.85	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 0.00936% African / African-American · 7/74,790 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00306% 49/1,603,926 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,684
Remaining individualsnot grpmax-eligible	0.00806%	12,403
Admixed American	0.00507%	19,735
European (non-Finnish)	0.00289%	34,590

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: APRT
Protein: p.Gly44Val
Coding: c.131G>T
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88811606 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 44: an α-helix

Full APRT 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

APRT p.Ala138Thr Uncertain significance ★★ ⚠ same condition
APRT p.Arg89Trp Uncertain significance ★★ ⚠ same condition
APRT p.Asp59Asn Uncertain significance ★★ ⚠ same condition
APRT p.Ile61Val Uncertain significance ★★ ⚠ same condition
APRT p.Leu129Arg Uncertain significance ★★ ⚠ same condition
APRT p.Pro17Ala Uncertain significance ★★ ⚠ same condition
APRT p.Ala116Val Uncertain significance ★ ⚠ same condition
APRT p.Asp3Gly 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/aprt-p-gly44val (accessed [today's date]).

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