Is APMAP p.Pro177Thr (c.529C>A) pathogenic?

APMAP p.Pro177Thr (c.529C>A) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.2026); Ultra-rare (popmax 0.0165%, mid).

How common is APMAP p.Pro177Thr (c.529C>A) in the general population?

APMAP p.Pro177Thr (c.529C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about APMAP p.Pro177Thr (c.529C>A)?

AlphaMissense predicts likely benign (score 0.2026) — an in-silico prediction, not a clinical call.

APMAP p.Pro177Thr

c.529C>A · VCV4641677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2026 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2026	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Pangolin	Δ0.27	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	24.6	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 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
European (non-Finnish)	0.00017%	589,647

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.Pro177Thr
Coding: c.529C>A
MANE Select: NM_020531
Type: single nucleotide variant
Location: chr20:24971469 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.60

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

Similar variants

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
APMAP p.Arg224Gln 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-pro177thr (accessed [today's date]).

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