Is PANK2 p.Cys313Phe (c.938G>T) pathogenic?

PANK2 p.Cys313Phe (c.938G>T) is classified Uncertain significance in PANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-22). AlphaMissense: likely pathogenic (0.9439); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with PANK2 p.Cys313Phe (c.938G>T)?

PANK2 p.Cys313Phe (c.938G>T) is associated with Inborn genetic diseases, retinitis pigmentosa (ClinVar).

How common is PANK2 p.Cys313Phe (c.938G>T) in the general population?

PANK2 p.Cys313Phe (c.938G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PANK2 p.Cys313Phe (c.938G>T)?

AlphaMissense predicts likely pathogenic (score 0.9439) — an in-silico prediction, not a clinical call.

PANK2 p.Cys313Phe

c.938G>T · rs779815683 · VCV1213870

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9439	likely pathogenic
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -12.76	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 29 kb · p 0.51 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C423F vs ClinVar C313F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,972 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,614,034 alleles · very rare exomes 24/1,461,886 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,986
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00186%	53,638

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: PANK2
Protein: p.Cys313Phe
Coding: c.938G>T
MANE Select: NM_001386393
dbSNP: rs779815683
Type: single nucleotide variant
Location: chr20:3912490 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 423 UniProt numbering: an α-helix

Full PANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

PANK2 c.1083-1G>T Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Gly411Arg Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Ala257Ser Uncertain significance ★★ ⚠ same condition
PANK2 p.Arg330His Uncertain significance ★★ ⚠ same condition
PANK2 p.Arg350Lys Uncertain significance ★★ ⚠ same condition
PANK2 p.Arg3Ser Uncertain significance ★★ ⚠ same condition
PANK2 p.Arg422Gln Uncertain significance ★★ ⚠ same condition
PANK2 p.Asn145Ser 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/pank2-p-cys313phe (accessed [today's date]).

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