Is PRUNE1 p.Ser321Phe (c.962C>T) pathogenic?

PRUNE1 p.Ser321Phe (c.962C>T) is classified Uncertain significance in PRUNE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.0307%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRUNE1 p.Ser321Phe (c.962C>T)?

PRUNE1 p.Ser321Phe (c.962C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRUNE1 p.Ser321Phe (c.962C>T) in the general population?

PRUNE1 p.Ser321Phe (c.962C>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about PRUNE1 p.Ser321Phe (c.962C>T)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

PRUNE1 p.Ser321Phe

c.962C>T · rs144150015 · VCV2372647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 26 kb · p 3.4e-05 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,908 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00155% 25/1,613,950 alleles · ultra-rare exomes 17/1,461,780 · genomes 8/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,257
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: PRUNE1
Protein: p.Ser321Phe
Coding: c.962C>T
MANE Select: NM_021222
dbSNP: rs144150015
Type: single nucleotide variant
Location: chr1:151033834 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.61
Residue 321: a UniProt-annotated variant site (in nmihba)

Full PRUNE1 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

Similar variants

PRUNE1 p.Asp87Asn Uncertain significance ★★ ⚠ same condition
PRUNE1 p.Ser391Asn Uncertain significance ★★ ⚠ same condition
PRUNE1 p.Thr311Met Uncertain significance ★★ ⚠ same condition
PRUNE1 p.Asp364Val Uncertain significance ★ ⚠ same condition
PRUNE1 p.Glu435Lys Uncertain significance ★ ⚠ same condition
PRUNE1 p.Ser370Ter Uncertain significance ★ same condition
PRUNE1 p.Ala221fs Pathogenic ★ same condition
PRUNE1 p.Asp3fs Pathogenic ★ 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/prune1-p-ser321phe (accessed [today's date]).

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