Is NAAA p.Arg300Trp (c.898C>T) pathogenic?

NAAA p.Arg300Trp (c.898C>T) is classified Uncertain significance in NAAA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: ambiguous (0.3432); Very rare (popmax 0.00932%, nfe).

How common is NAAA p.Arg300Trp (c.898C>T) in the general population?

NAAA p.Arg300Trp (c.898C>T) is very rare (popmax 0.00932%, nfe) (gnomAD).

What do computational predictors say about NAAA p.Arg300Trp (c.898C>T)?

AlphaMissense predicts ambiguous (score 0.3432) — an in-silico prediction, not a clinical call.

NAAA p.Arg300Trp

c.898C>T · rs529142915 · VCV3171921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3432	ambiguous
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -11.18	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.72 · 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 0.00932% European (non-Finnish) · 110/1,180,026 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00774% 125/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,728
African / African-American	0.00801%	12,487
South Asian	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Finnishnot grpmax-eligible	0.00312%	32,021
Admixed American	0.00167%	59,996

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: NAAA
Protein: p.Arg300Trp
Coding: c.898C>T
MANE Select: NM_014435
dbSNP: rs529142915
Type: single nucleotide variant
Location: chr4:75920742 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.67 · 2 PDB
Residue 300: an α-helix

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

Similar variants

NAAA p.Arg300Gln Uncertain significance ★ ⚠ same residue
NAAA c.667-7C>T Benign ★★ same type
NAAA p.Ile80= Likely benign ★★ same type
NAAA p.Thr262= Benign ★★ same type
NAAA p.Ala119Asp Uncertain significance ★ ⚠ same type
NAAA p.Ala314Val Uncertain significance ★ ⚠ same type
NAAA p.Arg100His Uncertain significance ★ ⚠ same type
NAAA p.Arg196Gln 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/naaa-p-arg300trp (accessed [today's date]).

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