Is CD70 p.Val130Met (c.388G>A) pathogenic?

CD70 p.Val130Met (c.388G>A) is classified Uncertain significance in CD70 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.6546); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Val130Met (c.388G>A)?

CD70 p.Val130Met (c.388G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Val130Met (c.388G>A) in the general population?

CD70 p.Val130Met (c.388G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD70 p.Val130Met (c.388G>A)?

AlphaMissense predicts likely pathogenic (score 0.6546) — an in-silico prediction, not a clinical call.

CD70 p.Val130Met

c.388G>A · rs548095306 · VCV2205040

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6546	likely pathogenic
REVEL	0.486	indeterminate
SaProt	LLR -9.61	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP 0.31, phastCons 0.051
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	18.94	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 · 1/6,050 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00291% 47/1,614,092 alleles · ultra-rare exomes 40/1,461,828 · genomes 7/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
East Asian	0.0111%	8,974
Admixed American	0.01%	10,003
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,251
African / African-American	0.00266%	37,525
European (non-Finnish)	0.00246%	40,690
Finnishnot grpmax-eligible	0.00156%	63,988

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: CD70
Protein: p.Val130Met
Coding: c.388G>A
MANE Select: NM_001252
dbSNP: rs548095306
Type: single nucleotide variant
Location: chr19:6586214 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 130: the thd domain; a β-strand

Full CD70 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

CD70 p.Leu23Phe Uncertain significance ★★ ⚠ same condition
CD70 p.Ser9Leu Uncertain significance ★★ ⚠ same condition
CD70 p.Thr118Met Uncertain significance ★★ ⚠ same condition
CD70 p.Thr119Met Uncertain significance ★★ ⚠ same condition
CD70 p.Ala129Gly Uncertain significance ★ ⚠ same condition
CD70 p.Ala136Pro Uncertain significance ★ ⚠ same condition
CD70 p.Ala136Thr Uncertain significance ★ ⚠ same condition
CD70 p.Arg192Ser 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/cd70-p-val130met (accessed [today's date]).

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