Is PRDM8 p.Ala249= (c.747C>T) pathogenic?

PRDM8 p.Ala249= (c.747C>T) is classified Likely benign in PRDM8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Absent from gnomAD v4.1.

How common is PRDM8 p.Ala249= (c.747C>T) in the general population?

PRDM8 p.Ala249= (c.747C>T) is absent from gnomAD v4.1 (gnomAD).

PRDM8 p.Ala249=

c.747C>T · rs1578263531 · VCV2654840

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.4	GERP -4.8
Overall
CADD	0.961	PHRED · no single calibrated threshold — expert panels disagree

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: PRDM8
Protein: p.Ala249=
Coding: c.747C>T
MANE Select: NM_001099403
dbSNP: rs1578263531
Type: single nucleotide variant
Location: chr4:80202209 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 55.64
Residue 249: the 'disordered' region

Full PRDM8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM8 p.Ala372Thr Uncertain significance ★★ ⚠ same type
PRDM8 p.Ala416Thr Uncertain significance ★★ ⚠ same type
PRDM8 p.Ala529Val Uncertain significance ★★ ⚠ same type
PRDM8 p.Ala540Ser Uncertain significance ★★ ⚠ same type
PRDM8 p.Ala541Ser Uncertain significance ★★ ⚠ same type
PRDM8 p.Ala546Val Uncertain significance ★★ ⚠ same type
PRDM8 p.Arg272Trp Uncertain significance ★★ ⚠ same type
PRDM8 p.Arg448Gln 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/prdm8-p-ala249 (accessed [today's date]).

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