Is PRDM13 p.His2= (c.6C>T) pathogenic?

PRDM13 p.His2= (c.6C>T) is classified Benign/Likely benign in PRDM13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Rare (popmax 0.651%, afr).

How common is PRDM13 p.His2= (c.6C>T) in the general population?

PRDM13 p.His2= (c.6C>T) is rare (popmax 0.651%, afr) (gnomAD).

PRDM13 p.His2=

c.6C>T · rs181938025 · VCV1170404

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.651%, afr)

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 0.049	GERP -1.6, phastCons 0.81
Overall
CADD	7.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.651% African / African-American · 488/74,938 alleles

Filtering AF 0.603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.585%

Overall 0.036% 579/1,609,344 alleles · rare exomes 303/1,456,982 · genomes 276/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.651%	154
Remaining individualsnot grpmax-eligible	0.0594%	1,683
Admixed American	0.0519%	1,927
South Asian	0.00441%	22,679
European (non-Finnish)	0.00161%	61,996

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: PRDM13
Protein: p.His2=
Coding: c.6C>T
MANE Select: NM_021620
dbSNP: rs181938025
Type: single nucleotide variant
Location: chr6:99607040 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 53.52
Residue 2: the set domain

Full PRDM13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM13 p.His2Gln Uncertain significance ★ ⚠ same residue
PRDM13 c.277-10T>G Uncertain significance ★★ same type
PRDM13 p.Ala231Val Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala258Val Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala298Pro Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala414Glu Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala510Thr Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala566Thr 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/prdm13-p-his2 (accessed [today's date]).

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