Is PRMT5 p.Ser608Phe (c.1823C>T) pathogenic?

PRMT5 p.Ser608Phe (c.1823C>T) is classified Uncertain significance in PRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.2148); Ultra-rare (popmax 0.0238%, nfe).

How common is PRMT5 p.Ser608Phe (c.1823C>T) in the general population?

PRMT5 p.Ser608Phe (c.1823C>T) is ultra-rare (popmax 0.0238%, nfe) (gnomAD).

What do computational predictors say about PRMT5 p.Ser608Phe (c.1823C>T)?

AlphaMissense predicts likely benign (score 0.2148) — an in-silico prediction, not a clinical call.

PRMT5 p.Ser608Phe

c.1823C>T · rs373166386 · VCV2387707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0238%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2148	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,028 bp · p 6.5e-25 · regional, not allelic
Overall
CADD	29.1	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 0.0238% European (non-Finnish) · 281/1,180,042 alleles

Filtering AF 0.0215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.018% 291/1,614,056 alleles · ultra-rare exomes 282/1,461,880 · genomes 9/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0238%	4,199
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.004%	24,972

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: PRMT5
Protein: p.Ser608Phe
Coding: c.1823C>T
MANE Select: NM_006109
dbSNP: rs373166386
Type: single nucleotide variant
Location: chr14:22920995 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.68 · 94 PDB
Residue 608: a β-strand; the sam-dependent mtase prmt-type domain; the 'beta barrel' region

Full PRMT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT5 p.His143= Benign ★★ same type
PRMT5 p.Leu81= Benign ★★ same type
PRMT5 p.Pro125= Benign ★★ same type
PRMT5 p.Ala552Ser Uncertain significance ★ ⚠ same type
PRMT5 p.Ala9Gly Uncertain significance ★ ⚠ same type
PRMT5 p.Arg377Gln Uncertain significance ★ ⚠ same type
PRMT5 p.Arg384Gln Uncertain significance ★ ⚠ same type
PRMT5 p.Arg385Gln 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/prmt5-p-ser608phe (accessed [today's date]).

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