Is PRMT7 p.Arg376Trp (c.1126C>T) pathogenic?

PRMT7 p.Arg376Trp (c.1126C>T) is classified Uncertain significance in PRMT7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.7097); Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRMT7 p.Arg376Trp (c.1126C>T)?

PRMT7 p.Arg376Trp (c.1126C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRMT7 p.Arg376Trp (c.1126C>T) in the general population?

PRMT7 p.Arg376Trp (c.1126C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about PRMT7 p.Arg376Trp (c.1126C>T)?

AlphaMissense predicts likely pathogenic (score 0.7097) — an in-silico prediction, not a clinical call.

PRMT7 p.Arg376Trp

c.1126C>T · VCV3369269

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7097	likely pathogenic
REVEL	0.652	pathogenic-leaning
SaProt	LLR -12.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	28.8	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 0.0213% African / African-American · 16/75,042 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00558% 90/1,614,192 alleles · ultra-rare exomes 67/1,461,878 · genomes 23/152,314 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.439%	228
African / African-Americangrpmax	0.0213%	4,690
Admixed American	0.0183%	5,457
East Asian	0.0156%	6,411
Remaining individualsnot grpmax-eligible	0.0064%	15,628
European (non-Finnish)	0.0039%	25,653
South Asian	0.0022%	45,544

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg376Trp
Coding: c.1126C>T
MANE Select: NM_019023
Type: single nucleotide variant
Location: chr16:68346215 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 376: the sam-dependent mtase prmt-type 2 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.Arg376Leu Uncertain significance ★ ⚠ same residue
PRMT7 p.Arg376= Likely benign ★ same residue
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

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-arg376trp (accessed [today's date]).

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