Is CD70 p.His124Arg (c.371A>G) pathogenic?

CD70 p.His124Arg (c.371A>G) is classified Uncertain significance in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-19). AlphaMissense: likely benign (0.0981); Absent from gnomAD v4.1.

How common is CD70 p.His124Arg (c.371A>G) in the general population?

CD70 p.His124Arg (c.371A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD70 p.His124Arg (c.371A>G)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

CD70 p.His124Arg

c.371A>G · VCV4082404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0981	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -2.09	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 -9	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	0.004	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

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: CD70
Protein: p.His124Arg
Coding: c.371A>G
MANE Select: NM_001252
Type: single nucleotide variant
Location: chr19:6586231 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 124: the thd domain; a disulfide bond

Full CD70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD70 p.His124Gln Uncertain significance ★ ⚠ same residue
CD70 p.Leu23Phe Uncertain significance ★★ ⚠ same type
CD70 p.Ser146Ile Uncertain significance ★★ ⚠ same type
CD70 p.Ser9Leu Uncertain significance ★★ ⚠ same type
CD70 p.Thr118Met Uncertain significance ★★ ⚠ same type
CD70 p.Thr119Met Uncertain significance ★★ ⚠ same type
CD70 p.Val130Met Uncertain significance ★★ ⚠ same type
CD70 p.Cys115= Benign ★★ 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/cd70-p-his124arg (accessed [today's date]).

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