Is PRDM6 p.Ser511Pro (c.1531T>C) pathogenic?

PRDM6 p.Ser511Pro (c.1531T>C) is classified Uncertain significance in PRDM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.6563); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRDM6 p.Ser511Pro (c.1531T>C)?

PRDM6 p.Ser511Pro (c.1531T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PRDM6 p.Ser511Pro (c.1531T>C) in the general population?

PRDM6 p.Ser511Pro (c.1531T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM6 p.Ser511Pro (c.1531T>C)?

AlphaMissense predicts likely pathogenic (score 0.6563) — an in-silico prediction, not a clinical call.

PRDM6 p.Ser511Pro

c.1531T>C · rs2479414106 · VCV3218450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6563 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6563	likely pathogenic
REVEL	0.409	indeterminate
SaProt	LLR -7.25	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 16 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM6
Protein: p.Ser511Pro
Coding: c.1531T>C
MANE Select: NM_001136239
dbSNP: rs2479414106
Type: single nucleotide variant
Location: chr5:123180181 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 57.72

Full PRDM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDM6 p.Leu26Phe Uncertain significance ★★ ⚠ same condition
PRDM6 p.Lys149Met Uncertain significance ★★ ⚠ same condition
PRDM6 p.Pro56= Likely benign ★★ same condition
PRDM6 p.Ala101Pro Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala102Pro Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala124Val Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala141Thr Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala232Thr Uncertain significance ★ ⚠ 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/prdm6-p-ser511pro (accessed [today's date]).

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