Is PRDM7 p.Arg50His (c.149G>A) pathogenic?

PRDM7 p.Arg50His (c.149G>A) is classified Uncertain significance in PRDM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1458); Ultra-rare (popmax 0.0165%, mid).

How common is PRDM7 p.Arg50His (c.149G>A) in the general population?

PRDM7 p.Arg50His (c.149G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PRDM7 p.Arg50His (c.149G>A)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

PRDM7 p.Arg50His

c.149G>A · rs536731786 · VCV3218460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -12.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.22	donor loss, 40 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.18
Regional constraint	o/e 0.96	unconstrained · MANE · 18 kb · p 0.35 · regional, not allelic
Overall
CADD	18.72	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00142% 23/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.0032%	31,255
African / African-American	0.00267%	37,518
South Asian	0.0011%	91,082
European (non-Finnish)	0.00102%	98,337

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: PRDM7
Protein: p.Arg50His
Coding: c.149G>A
MANE Select: NM_001098173
dbSNP: rs536731786
Type: single nucleotide variant
Location: chr16:90075395 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.59
Residue 50: the krab-related domain

Full PRDM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM7 p.Ala122Val Uncertain significance ★ ⚠ same type
PRDM7 p.Ala264Val Uncertain significance ★ ⚠ same type
PRDM7 p.Ala313Pro Uncertain significance ★ ⚠ same type
PRDM7 p.Ala322Asp Uncertain significance ★ ⚠ same type
PRDM7 p.Ala68Gly Uncertain significance ★ ⚠ same type
PRDM7 p.Arg237Cys Uncertain significance ★ ⚠ same type
PRDM7 p.Arg323Gln Uncertain significance ★ ⚠ same type
PRDM7 p.Arg323Trp 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/prdm7-p-arg50his (accessed [today's date]).

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