Is TTN p.Pro2201Ser (c.6601C>T) pathogenic?

TTN p.Pro2201Ser (c.6601C>T) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2016-05-09). AlphaMissense: ambiguous (0.5304); Very rare (popmax 0.00769%, sas); Associated with cardiomyopathy.

What condition is associated with TTN p.Pro2201Ser (c.6601C>T)?

TTN p.Pro2201Ser (c.6601C>T) is associated with cardiomyopathy (ClinVar).

How common is TTN p.Pro2201Ser (c.6601C>T) in the general population?

TTN p.Pro2201Ser (c.6601C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about TTN p.Pro2201Ser (c.6601C>T)?

AlphaMissense predicts ambiguous (score 0.5304) — an in-silico prediction, not a clinical call.

TTN p.Pro2201Ser

c.6601C>T · rs763426070 · VCV626700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.5304	ambiguous
REVEL	0.418	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 141 kb · p 0.23 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000496% 8/1,613,990 alleles · very rare exomes 7/1,461,748 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
European (non-Finnish)	8.47e-05%	1,179,976

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: TTN
Protein: p.Pro2201Ser
Coding: c.6601C>T
MANE Select: NM_001267550
dbSNP: rs763426070
Type: single nucleotide variant
Location: chr2:178775110 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 2201: the ig-like 11 domain

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

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTN c.2775+1G>T Likely pathogenic ★★ same condition
TTN c.54811+1G>A Likely pathogenic ★★ same condition
TTN c.58732+2T>C Likely pathogenic ★★ same condition
TTN c.67349-2A>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.86821+2T>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.97492+1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN p.Arg14069Ter Pathogenic/Likely pathogenic ★★ same condition
TTN p.Arg14079Ter Pathogenic/Likely pathogenic ★★ 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/ttn-p-pro2201ser (accessed [today's date]).

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