Is AP1AR p.Ser29Phe (c.86C>T) pathogenic?

AP1AR p.Ser29Phe (c.86C>T) is classified Uncertain significance in AP1AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.8823); Ultra-rare (popmax 0.0269%, eas).

How common is AP1AR p.Ser29Phe (c.86C>T) in the general population?

AP1AR p.Ser29Phe (c.86C>T) is ultra-rare (popmax 0.0269%, eas) (gnomAD).

What do computational predictors say about AP1AR p.Ser29Phe (c.86C>T)?

AlphaMissense predicts likely pathogenic (score 0.8823) — an in-silico prediction, not a clinical call.

AP1AR p.Ser29Phe

c.86C>T · VCV3300175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8823	likely pathogenic
REVEL	0.328	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 35 kb · p 0.0024 · regional, not allelic
Overall
CADD	28.1	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 0.0269% East Asian · 12/44,650 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00243% 39/1,608,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0269%	3,721
Remaining individualsnot grpmax-eligible	0.00642%	15,566
South Asian	0.00332%	30,101
European (non-Finnish)	0.0017%	58,863

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.Ser29Phe
Coding: c.86C>T
MANE Select: NM_018569
Type: single nucleotide variant
Location: chr4:112253210 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.16
Residue 29: a modified residue (phosphoserine)

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-ser29phe (accessed [today's date]).

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