Is CTSF p.Arg71Trp (c.211C>T) pathogenic?

CTSF p.Arg71Trp (c.211C>T) is classified Uncertain significance in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.1707); Very rare (popmax 0.00216%, amr).

How common is CTSF p.Arg71Trp (c.211C>T) in the general population?

CTSF p.Arg71Trp (c.211C>T) is very rare (popmax 0.00216%, amr) (gnomAD).

What do computational predictors say about CTSF p.Arg71Trp (c.211C>T)?

AlphaMissense predicts likely benign (score 0.1707) — an in-silico prediction, not a clinical call.

CTSF p.Arg71Trp

c.211C>T · VCV3893482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00216%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1707	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -10.83	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,550 bp · p 0.69 · regional, not allelic
Overall
CADD	29.9	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 0.00216% Admixed American · 1/46,334 alleles

Filtering AF 0.000718% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000562%

Overall 0.00107% 16/1,499,856 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00216%	46,334
Remaining individualsnot grpmax-eligible	0.00173%	57,946
European (non-Finnish)	0.00124%	80,822

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: CTSF
Protein: p.Arg71Trp
Coding: c.211C>T
MANE Select: NM_003793
Type: single nucleotide variant
Location: chr11:66568276 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB

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

Similar variants

CTSF c.1045+1G>T Likely pathogenic ★★ same type
CTSF p.Arg217Ter Pathogenic ★★ same type
CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same type
CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same type
CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same type
CTSF p.Arg196Trp Uncertain significance ★★ ⚠ same type
CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same type
CTSF p.Arg413Cys 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/ctsf-p-arg71trp (accessed [today's date]).

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