Is PRMT7 p.Pro353Leu (c.1058C>T) pathogenic?

PRMT7 p.Pro353Leu (c.1058C>T) is classified Uncertain significance in PRMT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.0158%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRMT7 p.Pro353Leu (c.1058C>T)?

PRMT7 p.Pro353Leu (c.1058C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRMT7 p.Pro353Leu (c.1058C>T) in the general population?

PRMT7 p.Pro353Leu (c.1058C>T) is ultra-rare (popmax 0.0158%, nfe) (gnomAD).

What do computational predictors say about PRMT7 p.Pro353Leu (c.1058C>T)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

PRMT7 p.Pro353Leu

c.1058C>T · VCV3310251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.6, phastCons 0.007
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	14.38	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

Grpmax group 0.0158% European (non-Finnish) · 186/1,180,042 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.0116% 187/1,613,510 alleles · ultra-rare exomes 186/1,461,362 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0158%	6,344
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Pro353Leu
Coding: c.1058C>T
MANE Select: NM_019023
Type: single nucleotide variant
Location: chr16:68346147 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19

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-pro353leu (accessed [today's date]).

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