Is PRMT7 p.Arg360Cys (c.1078C>T) pathogenic?

PRMT7 p.Arg360Cys (c.1078C>T) is classified Uncertain significance in PRMT7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-08-04). AlphaMissense: likely benign (0.0618); Ultra-rare (popmax 0.0164%, mid); Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Arg360Cys (c.1078C>T)?

PRMT7 p.Arg360Cys (c.1078C>T) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Arg360Cys (c.1078C>T) in the general population?

PRMT7 p.Arg360Cys (c.1078C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about PRMT7 p.Arg360Cys (c.1078C>T)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

PRMT7 p.Arg360Cys

c.1078C>T · rs775110866 · VCV1032052

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short stature-brachydactyly-obesity-global developmental delay syndrome

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -1.5
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	13.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00242% 39/1,613,842 alleles · ultra-rare exomes 36/1,461,758 · genomes 3/152,084 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00534%	18,724
East Asian	0.00446%	22,440
South Asian	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.0022%	45,386
Admixed American	0.00167%	59,984

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.Arg360Cys
Coding: c.1078C>T
MANE Select: NM_019023
dbSNP: rs775110866
Type: single nucleotide variant
Location: chr16:68346167 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 360: 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.Arg360His Benign/Likely benign ★★ 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
PRMT7 p.Tyr159Ter 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-arg360cys (accessed [today's date]).

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