Is CD7 p.Arg229Cys (c.685C>T) pathogenic?

CD7 p.Arg229Cys (c.685C>T) is classified Uncertain significance in CD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.2111); Very rare (popmax 0.00401%, afr).

How common is CD7 p.Arg229Cys (c.685C>T) in the general population?

CD7 p.Arg229Cys (c.685C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CD7 p.Arg229Cys (c.685C>T)?

AlphaMissense predicts likely benign (score 0.2111) — an in-silico prediction, not a clinical call.

CD7 p.Arg229Cys

c.685C>T · VCV4223004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2111	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -8.51	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 -0.77	GERP -1.5
Regional constraint	o/e 0.89	unconstrained · MANE · 2,171 bp · p 0.046 · regional, not allelic
Overall
CADD	8.701	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

Grpmax group 0.00401% African / African-American · 3/74,852 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000868% 14/1,613,242 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,951
South Asian	0.0011%	91,076
European (non-Finnish)	0.000848%	117,981

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.Arg229Cys
Coding: c.685C>T
MANE Select: NM_006137
Type: single nucleotide variant
Location: chr17:82315359 (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.Arg229Ser Uncertain significance ★ ⚠ same residue
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

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-arg229cys (accessed [today's date]).

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