Is NAAA p.Thr262= (c.786G>A) pathogenic?

NAAA p.Thr262= (c.786G>A) is classified Benign in NAAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). Common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele.

NAAA p.Thr262=

Q: How common is NAAA p.Thr262= (c.786G>A) in the general population?

NAAA p.Thr262= (c.786G>A) is common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.786G>A · rs61736789 · VCV785096

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.4
Overall
CADD	2.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.28% African / African-American · 5,440/74,764 alleles

Filtering AF 7.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.05%

Overall 0.389% 6,263/1,611,722 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.28%	14
Remaining individualsnot grpmax-eligible	0.54%	185
Admixed American	0.509%	196
Middle Eastern	0.314%	319
Ashkenazi Jewishnot grpmax-eligible	0.0914%	1,094
South Asian	0.0177%	5,659
European (non-Finnish)	0.0101%	9,912
East Asian	0.00891%	11,222

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.Thr262=
Coding: c.786G>A
MANE Select: NM_014435
dbSNP: rs61736789
Type: single nucleotide variant
Location: chr4:75921004 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.67 · 2 PDB
Residue 262: a β-strand

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.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
NAAA p.Arg300Gln 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-thr262 (accessed [today's date]).

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