Is APMAP p.Asp167Asn (c.499G>A) pathogenic?

APMAP p.Asp167Asn (c.499G>A) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.8241); Ultra-rare (popmax 0.0303%, nfe).

How common is APMAP p.Asp167Asn (c.499G>A) in the general population?

APMAP p.Asp167Asn (c.499G>A) is ultra-rare (popmax 0.0303%, nfe) (gnomAD).

What do computational predictors say about APMAP p.Asp167Asn (c.499G>A)?

AlphaMissense predicts likely pathogenic (score 0.8241) — an in-silico prediction, not a clinical call.

APMAP p.Asp167Asn

c.499G>A · rs200046619 · VCV2355508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8241 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0303%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8241	likely pathogenic
REVEL	0.522	indeterminate
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0303% European (non-Finnish) · 357/1,180,008 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.0234% 377/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0303%	3,305
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.004%	24,975
Admixed American	0.00333%	30,006
South Asian	0.0011%	91,090

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.Asp167Asn
Coding: c.499G>A
MANE Select: NM_020531
dbSNP: rs200046619
Type: single nucleotide variant
Location: chr20:24971499 (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-asp167asn (accessed [today's date]).

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