Is PRUNE1 p.Ser15Phe (c.44C>T) pathogenic?

PRUNE1 p.Ser15Phe (c.44C>T) is classified Benign/Likely benign in PRUNE1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.1036); Low-frequency (popmax 1.03%, afr).

How common is PRUNE1 p.Ser15Phe (c.44C>T) in the general population?

PRUNE1 p.Ser15Phe (c.44C>T) is low-frequency (popmax 1.03%, afr) (gnomAD).

What do computational predictors say about PRUNE1 p.Ser15Phe (c.44C>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

PRUNE1 p.Ser15Phe

c.44C>T · rs149560167 · VCV2050841

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -10.40	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 4.4	GERP 0.48, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 26 kb · p 3.4e-05 · regional, not allelic
Overall
CADD	23.5	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 1.03% African / African-American · 764/74,198 alleles

Filtering AF 0.969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.945%

Overall 0.0569% 901/1,582,244 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.03%	97
Admixed American	0.122%	819
Remaining individualsnot grpmax-eligible	0.0782%	1,279
Middle Eastern	0.0334%	2,991
South Asian	0.00443%	22,569
European (non-Finnish)	0.000868%	115,172

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.Ser15Phe
Coding: c.44C>T
MANE Select: NM_021222
dbSNP: rs149560167
Type: single nucleotide variant
Location: chr1:151017816 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.61

Full PRUNE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRUNE1 c.132+2T>C Pathogenic ★★ same type
PRUNE1 c.521-2A>G Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Arg128Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
PRUNE1 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Asp106Asn Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Asp30Asn Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Ala39Pro Uncertain significance ★★ ⚠ same type
PRUNE1 p.Asp87Asn Uncertain significance ★★ ⚠ 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/prune1-p-ser15phe (accessed [today's date]).

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