Is GNAT2 p.Ala71= (c.213T>G) pathogenic?

GNAT2 p.Ala71= (c.213T>G) is classified Conflicting classifications of pathogenicity in GNAT2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-24). Rare (popmax 0.182%, sas); Associated with achromatopsia 4.

What condition is associated with GNAT2 p.Ala71= (c.213T>G)?

GNAT2 p.Ala71= (c.213T>G) is associated with achromatopsia 4 (ClinVar).

How common is GNAT2 p.Ala71= (c.213T>G) in the general population?

GNAT2 p.Ala71= (c.213T>G) is rare (popmax 0.182%, sas) (gnomAD).

How is Achromatopsia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GNAT2 p.Ala71=

c.213T>G · rs577261001 · VCV874700

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.182%, sas)

Conditions

achromatopsia 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -3.8, phastCons 0.98
Overall
CADD	10.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.182% South Asian · 166/91,080 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.011% 177/1,613,368 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.182%	549
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,038

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: GNAT2
Protein: p.Ala71=
Coding: c.213T>G
MANE Select: NM_001377295
dbSNP: rs577261001
Type: single nucleotide variant
Location: chr1:109610130 (GRCh38)
Gene constraint: LOEUF 1.176 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21 · 2 PDB
Residue 71: the g-alpha domain

Full GNAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

achromatopsia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Achromatopsia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

GNAT2 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same condition
GNAT2 p.Arg161Ter Pathogenic ★★ same condition
GNAT2 p.Arg313Ter Pathogenic ★★ same condition
GNAT2 c.-53-78G>A Uncertain significance ★★ same condition
GNAT2 p.Arg242Cys Uncertain significance ★★ ⚠ same condition
GNAT2 p.Asp94Ala Uncertain significance ★★ ⚠ same condition
GNAT2 p.Glu239Lys Uncertain significance ★★ ⚠ same condition
GNAT2 p.His282Pro Uncertain significance ★★ ⚠ same condition

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/gnat2-p-ala71 (accessed [today's date]).

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