Is PRDM5 p.Ser356Pro (c.1066T>C) pathogenic?

PRDM5 p.Ser356Pro (c.1066T>C) is classified Likely benign in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.9197); Very rare (popmax 0.00334%, amr).

How common is PRDM5 p.Ser356Pro (c.1066T>C) in the general population?

PRDM5 p.Ser356Pro (c.1066T>C) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about PRDM5 p.Ser356Pro (c.1066T>C)?

AlphaMissense predicts likely pathogenic (score 0.9197) — an in-silico prediction, not a clinical call.

PRDM5 p.Ser356Pro

c.1066T>C · rs140634372 · VCV2785717

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9197 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9197	likely pathogenic
REVEL	0.409	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	26.4	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 0.00334% Admixed American · 2/59,956 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,612,480 alleles · very rare exomes 2/1,460,364 · genomes 0/152,116 · 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: PRDM5
Protein: p.Ser356Pro
Coding: c.1066T>C
MANE Select: NM_018699
dbSNP: rs140634372
Type: single nucleotide variant
Location: chr4:120798389 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB

Full PRDM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM5 p.Ser356Thr Benign/Likely benign ★★ same residue
PRDM5 c.1623+1G>A Likely pathogenic ★★ same type
PRDM5 c.865+1G>A Likely pathogenic ★★ same type
PRDM5 p.Arg232Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Arg346Ter Pathogenic ★★ same type
PRDM5 p.Gln420Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Gln556Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Glu103Ter Pathogenic/Likely pathogenic ★★ 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/prdm5-p-ser356pro (accessed [today's date]).

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