Is APMAP p.Arg120Trp (c.358C>T) pathogenic?

APMAP p.Arg120Trp (c.358C>T) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1236); Ultra-rare (popmax 0.0142%, nfe).

How common is APMAP p.Arg120Trp (c.358C>T) in the general population?

APMAP p.Arg120Trp (c.358C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

What do computational predictors say about APMAP p.Arg120Trp (c.358C>T)?

AlphaMissense predicts likely benign (score 0.1236) — an in-silico prediction, not a clinical call.

APMAP p.Arg120Trp

c.358C>T · rs185162626 · VCV2531322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1236 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1236	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -14.75	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.68, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	26.1	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 0.0142% European (non-Finnish) · 167/1,179,970 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0121% 196/1,614,066 alleles · ultra-rare exomes 189/1,461,816 · genomes 7/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0142%	7,066
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.011%	9,108
African / African-American	0.00933%	10,716
East Asian	0.00446%	22,446
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	60,028
Finnishnot grpmax-eligible	0.00156%	64,008

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.Arg120Trp
Coding: c.358C>T
MANE Select: NM_020531
dbSNP: rs185162626
Type: single nucleotide variant
Location: chr20:24973708 (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.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
APMAP p.Arg238Cys 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-arg120trp (accessed [today's date]).

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