Is CD7 p.Leu12Pro (c.35T>C) pathogenic?

CD7 p.Leu12Pro (c.35T>C) is classified Uncertain significance in CD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely benign (0.2388); Very rare (popmax 0.000603%, nfe).

How common is CD7 p.Leu12Pro (c.35T>C) in the general population?

CD7 p.Leu12Pro (c.35T>C) is very rare (popmax 0.000603%, nfe) (gnomAD).

What do computational predictors say about CD7 p.Leu12Pro (c.35T>C)?

AlphaMissense predicts likely benign (score 0.2388) — an in-silico prediction, not a clinical call.

CD7 p.Leu12Pro

c.35T>C · VCV4650696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000603%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2388	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -12.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.61	GERP 1.3
Regional constraint	o/e 0.89	unconstrained · MANE · 2,171 bp · p 0.046 · regional, not allelic
Overall
CADD	15.43	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 0.000603% European (non-Finnish) · 7/1,161,186 alleles

Filtering AF 0.000251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000161%

Overall 0.000492% 7/1,423,188 alleles · very rare

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: CD7
Protein: p.Leu12Pro
Coding: c.35T>C
MANE Select: NM_006137
Type: single nucleotide variant
Location: chr17:82317461 (GRCh38)
Gene constraint: LOEUF 1.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.51 · 2 PDB

Full CD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD7 p.Ala145Thr Uncertain significance ★ ⚠ same type
CD7 p.Ala154Asp Uncertain significance ★ ⚠ same type
CD7 p.Ala154Thr Uncertain significance ★ ⚠ same type
CD7 p.Ala15Val Uncertain significance ★ ⚠ same type
CD7 p.Ala17Ser Uncertain significance ★ ⚠ same type
CD7 p.Ala184Val Uncertain significance ★ ⚠ same type
CD7 p.Ala217Thr Uncertain significance ★ ⚠ same type
CD7 p.Ala218Thr 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/cd7-p-leu12pro (accessed [today's date]).

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