Is CD70 p.Leu171Phe (c.511C>T) pathogenic?

CD70 p.Leu171Phe (c.511C>T) is classified Uncertain significance in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely pathogenic (0.7469); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Leu171Phe (c.511C>T)?

CD70 p.Leu171Phe (c.511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Leu171Phe (c.511C>T) in the general population?

CD70 p.Leu171Phe (c.511C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD70 p.Leu171Phe (c.511C>T)?

AlphaMissense predicts likely pathogenic (score 0.7469) — an in-silico prediction, not a clinical call.

CD70 p.Leu171Phe

c.511C>T · rs2512811392 · VCV2250677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7469 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7469	likely pathogenic
REVEL	0.666	pathogenic-leaning
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	24.3	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

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.Leu171Phe
Coding: c.511C>T
MANE Select: NM_001252
dbSNP: rs2512811392
Type: single nucleotide variant
Location: chr19:6586091 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 171: 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.Val130Met 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

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-leu171phe (accessed [today's date]).

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