Is PRMT7 p.Arg358fs (c.1074_1075del) pathogenic?

PRMT7 p.Arg358fs (c.10741075del) is classified Likely pathogenic in PRMT7 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-06-01). Very rare (popmax 0.00333%, amr); Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Arg358fs (c.1074_1075del)?

PRMT7 p.Arg358fs (c.1074_1075del) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Arg358fs (c.1074_1075del) in the general population?

PRMT7 p.Arg358fs (c.1074_1075del) is very rare (popmax 0.00333%, amr) (gnomAD).

PRMT7 p.Arg358fs

c.1074_1075del · rs763953657 · VCV932173

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

short stature-brachydactyly-obesity-global developmental delay syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.4	GERP -5.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,010 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,900 alleles · very rare exomes 3/1,461,636 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,005
European (non-Finnish)	8.47e-05%	1,180,026

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.Arg358fs
Coding: c.1074_1075del
MANE Select: NM_019023
dbSNP: rs763953657
Type: Microsatellite
Location: chr16:68346158 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 358: the sam-dependent mtase prmt-type 2 domain

Full PRMT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature-brachydactyly-obesity-global developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRMT7 p.Glu144fs Pathogenic ★ same condition
PRMT7 p.Arg358Thr Uncertain significance ★ ⚠ same residue
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

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-arg358fs (accessed [today's date]).

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