Is PRMT7 p.Pro298Ala (c.892C>G) pathogenic?

PRMT7 p.Pro298Ala (c.892C>G) is classified Uncertain significance in PRMT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely pathogenic (0.7279); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRMT7 p.Pro298Ala (c.892C>G)?

PRMT7 p.Pro298Ala (c.892C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRMT7 p.Pro298Ala (c.892C>G) in the general population?

PRMT7 p.Pro298Ala (c.892C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PRMT7 p.Pro298Ala (c.892C>G)?

AlphaMissense predicts likely pathogenic (score 0.7279) — an in-silico prediction, not a clinical call.

PRMT7 p.Pro298Ala

c.892C>G · VCV3783467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7279	likely pathogenic
REVEL	0.634	indeterminate
SaProt	LLR -13.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	27.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,052 alleles

Overall 6.2e-05% 1/1,613,982 alleles · very rare exomes 1/1,461,744 · genomes 0/152,238 · joint denominator

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: PRMT7
Protein: p.Pro298Ala
Coding: c.892C>G
MANE Select: NM_019023
Type: single nucleotide variant
Location: chr16:68339933 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 298: the sam-dependent mtase prmt-type 1 domain

Full PRMT7 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

PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Ala162Thr Uncertain significance ★★ ⚠ same condition
PRMT7 p.Ala332Thr Uncertain significance ★★ ⚠ same condition
PRMT7 p.Ala519Thr Uncertain significance ★★ ⚠ same condition
PRMT7 p.Ala561Gly Uncertain significance ★★ ⚠ same condition
PRMT7 p.Arg177Gly Uncertain significance ★★ ⚠ same condition
PRMT7 p.Arg266Trp Uncertain significance ★★ ⚠ same condition
PRMT7 p.Arg311Trp 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/prmt7-p-pro298ala (accessed [today's date]).

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