Is AP1AR p.Ser79Pro (c.235T>C) pathogenic?

AP1AR p.Ser79Pro (c.235T>C) is classified Uncertain significance in AP1AR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: ambiguous (0.55); Very rare (popmax 0.000412%).

How common is AP1AR p.Ser79Pro (c.235T>C) in the general population?

AP1AR p.Ser79Pro (c.235T>C) is very rare (popmax 0.000412%) (gnomAD).

What do computational predictors say about AP1AR p.Ser79Pro (c.235T>C)?

AlphaMissense predicts ambiguous (score 0.55) — an in-silico prediction, not a clinical call.

AP1AR p.Ser79Pro

c.235T>C · rs1429408931 · VCV2278648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.55 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000412%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.55	ambiguous
REVEL	0.176	moderately benign-leaning
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.26, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 35 kb · p 0.0024 · regional, not allelic
Overall
CADD	24.6	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 0.000412%

Overall 0.000412% 6/1,455,008 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.Ser79Pro
Coding: c.235T>C
MANE Select: NM_018569
dbSNP: rs1429408931
Type: single nucleotide variant
Location: chr4:112260815 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.16
Residue 79: the 'interaction with ap1g1' region

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.Arg14Gly 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

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-ser79pro (accessed [today's date]).

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