Is PHRF1 p.Pro847Ala (c.2539C>G) pathogenic?

PHRF1 p.Pro847Ala (c.2539C>G) is classified Uncertain significance in PHRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0828); Absent from gnomAD v4.1.

How common is PHRF1 p.Pro847Ala (c.2539C>G) in the general population?

PHRF1 p.Pro847Ala (c.2539C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHRF1 p.Pro847Ala (c.2539C>G)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

PHRF1 p.Pro847Ala

c.2539C>G · rs776348620 · VCV2478080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 30 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	23.1	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

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: PHRF1
Protein: p.Pro847Ala
Coding: c.2539C>G
MANE Select: NM_001286581
dbSNP: rs776348620
Type: single nucleotide variant
Location: chr11:607995 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.11
Residue 847: the 'disordered' region

Full PHRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHRF1 p.Ala1355= Benign ★★ same type
PHRF1 p.Gly1209Arg Benign ★★ same type
PHRF1 p.Ser1168Leu Benign ★★ same type
PHRF1 p.Ser1457Gly Likely benign ★★ same type
PHRF1 p.Thr959= Likely benign ★★ same type
PHRF1 p.Ala114Ser Uncertain significance ★ ⚠ same type
PHRF1 p.Ala114Val Uncertain significance ★ ⚠ same type
PHRF1 p.Ala1197Ser 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/phrf1-p-pro847ala (accessed [today's date]).

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