Is AP1AR p.Arg14Gly (c.40C>G) pathogenic?

AP1AR p.Arg14Gly (c.40C>G) is classified Uncertain significance in AP1AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.2931); Very rare (popmax 8.84e-05%).

How common is AP1AR p.Arg14Gly (c.40C>G) in the general population?

AP1AR p.Arg14Gly (c.40C>G) is very rare (popmax 8.84e-05%) (gnomAD).

What do computational predictors say about AP1AR p.Arg14Gly (c.40C>G)?

AlphaMissense predicts likely benign (score 0.2931) — an in-silico prediction, not a clinical call.

AP1AR p.Arg14Gly

c.40C>G · rs900441049 · VCV3127419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2931	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -6.18	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 5.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 35 kb · p 0.0024 · regional, not allelic
Overall
CADD	25.5	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 8.84e-05%

Overall 8.84e-05% 1/1,131,054 alleles · very rare

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: AP1AR
Protein: p.Arg14Gly
Coding: c.40C>G
MANE Select: NM_018569
dbSNP: rs900441049
Type: single nucleotide variant
Location: chr4:112232131 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.16

Full AP1AR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1AR p.Val284= Benign ★★ same type
AP1AR p.Arg114His Uncertain significance ★ same type
AP1AR p.Arg123Gln Uncertain significance ★ ⚠ same type
AP1AR p.Arg302Gln Uncertain significance ★ ⚠ same type
AP1AR p.Asp86Glu Uncertain significance ★ ⚠ same type
AP1AR p.Asp86Gly Uncertain significance ★ ⚠ same type
AP1AR p.Gln21Arg Uncertain significance ★ ⚠ same type
AP1AR p.Gln92His Uncertain significance ★ ⚠ 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/ap1ar-p-arg14gly (accessed [today's date]).

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