Is CTSA p.Gly207Ala (c.620G>C) pathogenic?

CTSA p.Gly207Ala (c.620G>C) is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely pathogenic (0.5751); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTSA p.Gly207Ala (c.620G>C)?

CTSA p.Gly207Ala (c.620G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSA p.Gly207Ala (c.620G>C) in the general population?

CTSA p.Gly207Ala (c.620G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CTSA p.Gly207Ala (c.620G>C)?

AlphaMissense predicts likely pathogenic (score 0.5751) — an in-silico prediction, not a clinical call.

CTSA p.Gly207Ala

c.620G>C · VCV3837308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5751	likely pathogenic
REVEL	0.764	pathogenic-leaning
SaProt	LLR -12.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.59, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,710 bp · p 0.19 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000169% European (non-Finnish) · 2/1,180,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,838 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: CTSA
Protein: p.Gly207Ala
Coding: c.620G>C
MANE Select: NM_000308
Type: single nucleotide variant
Location: chr20:45893239 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 207: a disulfide bond

Full CTSA 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

CTSA p.Gly207= Likely benign ★ same residue
CTSA c.-17G>A Uncertain significance ★★ same condition
CTSA c.-41C>T Uncertain significance ★★ same condition
CTSA c.-6G>A Uncertain significance ★★ same condition
CTSA p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CTSA p.Arg372Cys Uncertain significance ★★ ⚠ same condition
CTSA p.Gly454Val Uncertain significance ★★ ⚠ same condition
CTSA p.Gly52Ser 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/ctsa-p-gly207ala (accessed [today's date]).

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