Is PANK2 p.Phe321Ser (c.962T>C) pathogenic?

PANK2 p.Phe321Ser (c.962T>C) is classified Pathogenic in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-01-01). AlphaMissense: likely pathogenic (0.9952); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with PANK2 p.Phe321Ser (c.962T>C)?

PANK2 p.Phe321Ser (c.962T>C) is associated with retinitis pigmentosa (ClinVar).

How common is PANK2 p.Phe321Ser (c.962T>C) in the general population?

PANK2 p.Phe321Ser (c.962T>C) is absent from gnomAD v4.1 (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 PANK2 p.Phe321Ser (c.962T>C)?

AlphaMissense predicts likely pathogenic (score 0.9952) — an in-silico prediction, not a clinical call.

PANK2 p.Phe321Ser

c.962T>C · rs863223343 · VCV191359

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9952	likely pathogenic ✓ concordant with ClinVar · top 9% in PANK2
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -11.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 29 kb · p 0.51 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F431S vs ClinVar F321S) — verify the residue.

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: PANK2
Protein: p.Phe321Ser
Coding: c.962T>C
MANE Select: NM_001386393
dbSNP: rs863223343
Type: single nucleotide variant
Location: chr20:3912514 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 431 UniProt numbering: an α-helix

Full PANK2 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

PANK2 p.Gly411Arg Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Cys313Phe Uncertain significance ★★ ⚠ same condition
PANK2 c.1082+1G>C Likely pathogenic ★★ same type
PANK2 c.1083-1G>T Pathogenic/Likely pathogenic ★★ same type
PANK2 c.1207-3C>G Pathogenic/Likely pathogenic ★★ same type
PANK2 c.299-1G>A Likely pathogenic ★★ same type
PANK2 c.905+1G>C Pathogenic ★★ same type
PANK2 c.-21G>T Pathogenic/Likely pathogenic ★★ 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/pank2-p-phe321ser (accessed [today's date]).

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