Is APMAP p.Pro12Thr (c.34C>A) pathogenic?

APMAP p.Pro12Thr (c.34C>A) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1202); Very rare (popmax 0.00975%, eas).

How common is APMAP p.Pro12Thr (c.34C>A) in the general population?

APMAP p.Pro12Thr (c.34C>A) is very rare (popmax 0.00975%, eas) (gnomAD).

What do computational predictors say about APMAP p.Pro12Thr (c.34C>A)?

AlphaMissense predicts likely benign (score 0.1202) — an in-silico prediction, not a clinical call.

APMAP p.Pro12Thr

c.34C>A · VCV3306831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00975%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1202	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.11	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 4.3	GERP 0.72, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	18.65	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 0.00975% East Asian · 4/41,038 alleles

Filtering AF 0.00327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00193%

Overall 0.000498% 7/1,406,616 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00975%	10,260
South Asian	0.00118%	84,924
European (non-Finnish)	0.000173%	577,221

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: APMAP
Protein: p.Pro12Thr
Coding: c.34C>A
MANE Select: NM_020531
Type: single nucleotide variant
Location: chr20:24992655 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.60
Residue 12: the 'disordered' region

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

Similar variants

APMAP p.Pro12Leu Uncertain significance ★ ⚠ same residue
APMAP p.Ala47Gly Uncertain significance ★ ⚠ same type
APMAP p.Arg120Trp Uncertain significance ★ ⚠ same type
APMAP p.Arg134Gln Uncertain significance ★ ⚠ same type
APMAP p.Arg134Pro Uncertain significance ★ ⚠ same type
APMAP p.Arg143Gly Uncertain significance ★ ⚠ same type
APMAP p.Arg156Cys Uncertain significance ★ ⚠ same type
APMAP p.Arg156His 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/apmap-p-pro12thr (accessed [today's date]).

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