Is PRMT7 p.Trp494Arg (c.1480T>C) pathogenic?

PRMT7 p.Trp494Arg (c.1480T>C) is classified Conflicting classifications of pathogenicity in PRMT7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.9914); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRMT7 p.Trp494Arg (c.1480T>C)?

PRMT7 p.Trp494Arg (c.1480T>C) is associated with Inborn genetic diseases, short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Trp494Arg (c.1480T>C) in the general population?

PRMT7 p.Trp494Arg (c.1480T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about PRMT7 p.Trp494Arg (c.1480T>C)?

AlphaMissense predicts likely pathogenic (score 0.9914) — an in-silico prediction, not a clinical call.

PRMT7 p.Trp494Arg

c.1480T>C · rs751670999 · VCV266021

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9914	likely pathogenic · top 2% in PRMT7
REVEL	0.598	indeterminate
SaProt	LLR -16.50	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 7.9	GERP 2.6, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,938 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00093% 15/1,613,368 alleles · very rare exomes 14/1,461,154 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,734
Admixed American	0.00167%	60,004
European (non-Finnish)	0.000847%	118,003

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.Trp494Arg
Coding: c.1480T>C
MANE Select: NM_019023
dbSNP: rs751670999
Type: single nucleotide variant
Location: chr16:68352314 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 494: a UniProt-annotated variant site (in sbidds); 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

Also linked: short stature-brachydactyly-obesity-global developmental delay syndrome

Similar variants

PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg390Ter Pathogenic ★★ same condition
PRMT7 p.Cys571Ter Pathogenic ★★ same condition
PRMT7 p.Gln323Ter Pathogenic ★★ same condition
PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Tyr159Ter Pathogenic ★★ same condition
PRMT7 p.Ala162Thr 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-trp494arg (accessed [today's date]).

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