Is PRMT6 p.Ala261Pro (c.781G>C) pathogenic?

PRMT6 p.Ala261Pro (c.781G>C) is classified Uncertain significance in PRMT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely benign (0.0645); Very rare (popmax 8.48e-05%, nfe).

How common is PRMT6 p.Ala261Pro (c.781G>C) in the general population?

PRMT6 p.Ala261Pro (c.781G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PRMT6 p.Ala261Pro (c.781G>C)?

AlphaMissense predicts likely benign (score 0.0645) — an in-silico prediction, not a clinical call.

PRMT6 p.Ala261Pro

c.781G>C · rs762278719 · VCV3218942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0645	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.08	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 0.78	GERP 0.016
Regional constraint	o/e 1.03	unconstrained · MANE · 1,124 bp · p 0.55 · regional, not allelic
Overall
CADD	13.2	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 8.48e-05% European (non-Finnish) · 1/1,179,742 alleles

Overall 6.2e-05% 1/1,613,178 alleles · very rare exomes 1/1,460,800 · genomes 0/152,378 · 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: PRMT6
Protein: p.Ala261Pro
Coding: c.781G>C
MANE Select: NM_018137
dbSNP: rs762278719
Type: single nucleotide variant
Location: chr1:107057496 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 13 PDB
Residue 261: the sam-dependent mtase prmt-type domain

Full PRMT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT6 p.Ala261Thr Uncertain significance ★ ⚠ same residue
PRMT6 p.Ala254Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Ala315Ser Uncertain significance ★ ⚠ same type
PRMT6 p.Ala321Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Arg347Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Arg347Trp Uncertain significance ★ ⚠ same type
PRMT6 p.Arg351His Uncertain significance ★ ⚠ same type
PRMT6 p.Arg352Leu 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/prmt6-p-ala261pro (accessed [today's date]).

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