Is PRPF6 p.Ala40= (c.120A>G) pathogenic?

PRPF6 p.Ala40= (c.120A>G) is classified Benign in PRPF6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.43%, afr); Associated with retinitis pigmentosa 60.

What condition is associated with PRPF6 p.Ala40= (c.120A>G)?

PRPF6 p.Ala40= (c.120A>G) is associated with retinitis pigmentosa 60, retinitis pigmentosa (ClinVar).

How common is PRPF6 p.Ala40= (c.120A>G) in the general population?

PRPF6 p.Ala40= (c.120A>G) is low-frequency (popmax 4.43%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF6 p.Ala40=

c.120A>G · rs34062309 · VCV339464

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.43%, afr)

Conditions

retinitis pigmentosa 60

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 -3	GERP -3.1
Overall
CADD	0.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.43% African / African-American · 3,327/75,052 alleles

Filtering AF 4.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.26%

Overall 0.299% 4,824/1,614,234 alleles · low-frequency exomes 2,829/1,461,888 · genomes 1,995/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.43%	23
Middle Eastern	0.677%	148
Admixed American	0.573%	174
Remaining individualsnot grpmax-eligible	0.472%	212
Ashkenazi Jewishnot grpmax-eligible	0.263%	380
European (non-Finnish)	0.0614%	1,630
South Asian	0.0143%	7,006
East Asian	0.00223%	44,888
Finnishnot grpmax-eligible	0.00156%	64,048

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: PRPF6
Protein: p.Ala40=
Coding: c.120A>G
MANE Select: NM_012469
dbSNP: rs34062309
Type: single nucleotide variant
Location: chr20:63983095 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 40: the 'disordered' region

Full PRPF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 60 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ same condition
PRPF6 p.Arg391Gln Uncertain significance ★★ ⚠ same condition
PRPF6 p.Arg703Trp Uncertain significance ★★ ⚠ same condition
PRPF6 p.His368Arg Uncertain significance ★★ ⚠ same condition
PRPF6 p.His865Tyr Uncertain significance ★★ ⚠ same condition
PRPF6 p.Ile919Val Uncertain significance ★★ ⚠ same condition
PRPF6 c.1186+13C>T Benign/Likely benign ★★ same condition
PRPF6 c.2340-11T>C Benign ★★ 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/prpf6-p-ala40 (accessed [today's date]).

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