Is PRMT7 p.Pro676Arg (c.2027C>G) pathogenic?

PRMT7 p.Pro676Arg (c.2027C>G) is classified Uncertain significance in PRMT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: ambiguous (0.4303); Ultra-rare (popmax 0.033%, mid).

How common is PRMT7 p.Pro676Arg (c.2027C>G) in the general population?

PRMT7 p.Pro676Arg (c.2027C>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about PRMT7 p.Pro676Arg (c.2027C>G)?

AlphaMissense predicts ambiguous (score 0.4303) — an in-silico prediction, not a clinical call.

PRMT7 p.Pro676Arg

c.2027C>G · VCV4930564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4303 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Computational evidence

Protein change
AlphaMissense	0.4303	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -8.86	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	23.4	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000558% 9/1,613,972 alleles · ultra-rare exomes 9/1,461,620 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0022%	45,541
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000339%	294,995

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.Pro676Arg
Coding: c.2027C>G
MANE Select: NM_019023
Type: single nucleotide variant
Location: chr16:68357172 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 676: the sam-dependent mtase prmt-type 2 domain

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

Similar variants

PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Arg390Ter Pathogenic ★★ same type
PRMT7 p.Cys571Ter Pathogenic ★★ same type
PRMT7 p.Gln323Ter Pathogenic ★★ same type
PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same type
PRMT7 p.Tyr159Ter Pathogenic ★★ same type
PRMT7 p.Ala162Thr Uncertain significance ★★ ⚠ same type

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-pro676arg (accessed [today's date]).

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