Is NAAA p.Pro73Ala (c.217C>G) pathogenic?

NAAA p.Pro73Ala (c.217C>G) is classified Uncertain significance in NAAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.2893); Absent from gnomAD v4.1.

How common is NAAA p.Pro73Ala (c.217C>G) in the general population?

NAAA p.Pro73Ala (c.217C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NAAA p.Pro73Ala (c.217C>G)?

AlphaMissense predicts likely benign (score 0.2893) — an in-silico prediction, not a clinical call.

NAAA p.Pro73Ala

c.217C>G · rs930269177 · VCV2336834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2893	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.72 · regional, not allelic
Overall
CADD	25.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NAAA
Protein: p.Pro73Ala
Coding: c.217C>G
MANE Select: NM_014435
dbSNP: rs930269177
Type: single nucleotide variant
Location: chr4:75940155 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.67 · 2 PDB

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

Similar variants

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
NAAA p.Arg256Trp 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-pro73ala (accessed [today's date]).

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