Is PRPF6 p.Arg367His (c.1100G>A) pathogenic?

PRPF6 p.Arg367His (c.1100G>A) is classified Uncertain significance in PRPF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.3174); Very rare (popmax 0.00223%, eas); Associated with retinitis pigmentosa.

What condition is associated with PRPF6 p.Arg367His (c.1100G>A)?

PRPF6 p.Arg367His (c.1100G>A) is associated with retinitis pigmentosa (ClinVar).

How common is PRPF6 p.Arg367His (c.1100G>A) in the general population?

PRPF6 p.Arg367His (c.1100G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about PRPF6 p.Arg367His (c.1100G>A)?

AlphaMissense predicts likely benign (score 0.3174) — an in-silico prediction, not a clinical call.

PRPF6 p.Arg367His

c.1100G>A · rs886056959 · VCV339468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.3174	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 23 kb · p 7.6e-14 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,192 alleles · very rare exomes 3/1,461,890 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
European (non-Finnish)	0.000169%	590,019

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.Arg367His
Coding: c.1100G>A
MANE Select: NM_012469
dbSNP: rs886056959
Type: single nucleotide variant
Location: chr20:64001153 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 367: an α-helix

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

Disease context

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

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.Arg367Cys Uncertain significance ★ same residue
PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ same condition
PRPF6 p.Arg703Trp Uncertain significance ★★ ⚠ same condition
PRPF6 p.His368Arg Uncertain significance ★★ ⚠ same condition
PRPF6 c.1186+13C>T Benign/Likely benign ★★ same condition
PRPF6 c.2340-11T>C Benign ★★ same condition
PRPF6 c.2431+15C>T Benign ★★ same condition
PRPF6 c.2546+15C>T Benign/Likely 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-arg367his (accessed [today's date]).

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