Is PRDM6 p.Pro117Ser (c.349C>T) pathogenic?

PRDM6 p.Pro117Ser (c.349C>T) is classified Uncertain significance in PRDM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.1867); Ultra-rare (popmax 0.0867%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRDM6 p.Pro117Ser (c.349C>T)?

PRDM6 p.Pro117Ser (c.349C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRDM6 p.Pro117Ser (c.349C>T) in the general population?

PRDM6 p.Pro117Ser (c.349C>T) is ultra-rare (popmax 0.0867%, nfe) (gnomAD).

What do computational predictors say about PRDM6 p.Pro117Ser (c.349C>T)?

AlphaMissense predicts likely benign (score 0.1867) — an in-silico prediction, not a clinical call.

PRDM6 p.Pro117Ser

c.349C>T · rs753024723 · VCV2346381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1867	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.55	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 7.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 81 kb · p 0.0014 · regional, not allelic
Overall
CADD	22.2	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 0.0867% European (non-Finnish) · 968/1,117,084 alleles

Filtering AF 0.082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0803%

Overall 0.0695% 1,023/1,472,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0867%	1,154
Finnishnot grpmax-eligible	0.0494%	2,026
Remaining individualsnot grpmax-eligible	0.0335%	2,989
Admixed American	0.0164%	6,112
African / African-American	0.00881%	11,349
South Asian	0.00129%	77,700

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: PRDM6
Protein: p.Pro117Ser
Coding: c.349C>T
MANE Select: NM_001136239
dbSNP: rs753024723
Type: single nucleotide variant
Location: chr5:123090363 (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-pro117ser (accessed [today's date]).

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