Is CTTN p.Asp527= (c.1581C>T) pathogenic?

CTTN p.Asp527= (c.1581C>T) is classified Likely benign in CTTN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Very rare (popmax 0.00924%, nfe).

How common is CTTN p.Asp527= (c.1581C>T) in the general population?

CTTN p.Asp527= (c.1581C>T) is very rare (popmax 0.00924%, nfe) (gnomAD).

CTTN p.Asp527=

c.1581C>T · rs772572367 · VCV2642067

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00924%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.3
Overall
CADD	0.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00924% European (non-Finnish) · 109/1,180,020 alleles

Filtering AF 0.00782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00731% 118/1,613,832 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00924%	10,826
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00157%	63,886
South Asian	0.0011%	91,082

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: CTTN
Protein: p.Asp527=
Coding: c.1581C>T
MANE Select: NM_005231
dbSNP: rs772572367
Type: single nucleotide variant
Location: chr11:70435090 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.11 · 5 PDB
Residue 527: a β-strand; the sh3 domain

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

Similar variants

CTTN p.Val312= Benign ★★ same type
CTTN p.Val340Gly Likely benign ★★ same type
CTTN c.*1144C>G Uncertain significance ★ same type
CTTN c.*1145C>T Uncertain significance ★ same type
CTTN c.*1154G>A Uncertain significance ★ same type
CTTN c.*1164C>T Uncertain significance ★ same type
CTTN c.*1167C>T Uncertain significance ★ same type
CTTN c.*1173G>A 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/cttn-p-asp527 (accessed [today's date]).

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