Is APMAP p.Val17Ala (c.50T>C) pathogenic?

APMAP p.Val17Ala (c.50T>C) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely benign (0.1827); Ultra-rare (popmax 0.0105%, sas).

How common is APMAP p.Val17Ala (c.50T>C) in the general population?

APMAP p.Val17Ala (c.50T>C) is ultra-rare (popmax 0.0105%, sas) (gnomAD).

What do computational predictors say about APMAP p.Val17Ala (c.50T>C)?

AlphaMissense predicts likely benign (score 0.1827) — an in-silico prediction, not a clinical call.

APMAP p.Val17Ala

c.50T>C · rs750026402 · VCV2396052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1827	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -5.41	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	22.0	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 0.0105% South Asian · 9/85,574 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00407%

Overall 0.000701% 11/1,568,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0105%	9,508
Remaining individualsnot grpmax-eligible	0.00165%	60,592
European (non-Finnish)	8.63e-05%	1,158,489

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.Val17Ala
Coding: c.50T>C
MANE Select: NM_020531
dbSNP: rs750026402
Type: single nucleotide variant
Location: chr20:24992639 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.60
Residue 17: the 'disordered' region

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-val17ala (accessed [today's date]).

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