Is PRMT7 p.Asp546= (c.1638C>T) pathogenic?

PRMT7 p.Asp546= (c.1638C>T) is classified Benign in PRMT7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Asp546= (c.1638C>T)?

PRMT7 p.Asp546= (c.1638C>T) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

PRMT7 p.Asp546=

Q: How common is PRMT7 p.Asp546= (c.1638C>T) in the general population?

PRMT7 p.Asp546= (c.1638C>T) is common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1638C>T · rs61746794 · VCV1304690

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -2, phastCons 0.019
Overall
CADD	12.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.4% African / African-American · 12,044/73,342 alleles

Filtering AF 16.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.1%

Overall 12% 190,141/1,584,450 alleles · common exomes 170,029/1,432,260 · genomes 20,112/152,190 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	18.9%	5
Finnishnot grpmax-eligible	16.7%	6
African / African-Americangrpmax	16.4%	6
South Asian	16.3%	6
Ashkenazi Jewishnot grpmax-eligible	15%	7
Middle Eastern	12.7%	8
Remaining individualsnot grpmax-eligible	11.8%	8
European (non-Finnish)	11.4%	9
Admixed American	7.86%	13
East Asian	7.29%	14

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.Asp546=
Coding: c.1638C>T
MANE Select: NM_019023
dbSNP: rs61746794
Type: single nucleotide variant
Location: chr16:68353554 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 546: 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 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.Arg360Cys 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-asp546 (accessed [today's date]).

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