Is PRMT7 p.Val416fs (c.1239_1246dup) pathogenic?

PRMT7 p.Val416fs (c.12391246dup) is classified Pathogenic in PRMT7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-01). Very rare (popmax 0.00195%, amr); Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Val416fs (c.1239_1246dup)?

PRMT7 p.Val416fs (c.1239_1246dup) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Val416fs (c.1239_1246dup) in the general population?

PRMT7 p.Val416fs (c.1239_1246dup) is very rare (popmax 0.00195%, amr) (gnomAD).

PRMT7 p.Val416fs

c.1239_1246dup · rs1567721991 · VCV522593

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00195%, 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 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% Admixed American · 1/51,342 alleles

Overall 6.44e-05% 1/1,553,438 alleles · very rare exomes 1/1,401,092 · genomes 0/152,346 · 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.Val416fs
Coding: c.1239_1246dup
MANE Select: NM_019023
dbSNP: rs1567721991
Type: Duplication
Location: chr16:68347257 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 416: 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.Asp501fs Likely pathogenic ★ same condition
PRMT7 p.Glu153fs Likely pathogenic ★ same condition
PRMT7 p.His447Ter Likely pathogenic ★ same condition
PRMT7 p.Leu448fs Likely pathogenic ★ same condition
PRMT7 p.Phe583fs Likely pathogenic ★ same condition
PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg390Ter 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-val416fs (accessed [today's date]).

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