Is TTN p.Arg26331Gln (c.78992G>A) pathogenic?

TTN p.Arg26331Gln (c.78992G>A) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-26). AlphaMissense: likely pathogenic (0.8051); Very rare (popmax 0.00935%, afr).

How common is TTN p.Arg26331Gln (c.78992G>A) in the general population?

TTN p.Arg26331Gln (c.78992G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about TTN p.Arg26331Gln (c.78992G>A)?

AlphaMissense predicts likely pathogenic (score 0.8051) — an in-silico prediction, not a clinical call.

TTN p.Arg26331Gln

c.78992G>A · rs758190406 · VCV1013432

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8051 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Computational evidence

Protein change
AlphaMissense	0.8051	likely pathogenic
REVEL	0.408	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 75 kb · p 3.1e-23 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R24690Q vs ClinVar R26331Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,876 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00161% 26/1,613,366 alleles · very rare exomes 20/1,461,288 · genomes 6/152,078 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,697
South Asian	0.00659%	15,177
Remaining individualsnot grpmax-eligible	0.0048%	20,813
European (non-Finnish)	0.000848%	117,960

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.Arg26331Gln
Coding: c.78992G>A
MANE Select: NM_001267550
dbSNP: rs758190406
Type: single nucleotide variant
Location: chr2:178567140 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

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

Similar variants

TTN p.Arg26331Ter Pathogenic/Likely pathogenic ★★ same residue
TTN p.Arg26331= Conflicting classifications of pathogenicity ★ same residue
TTN c.100171+1G>A Likely pathogenic ★★ same type
TTN c.100766-1G>T Likely pathogenic ★★ same type
TTN c.100766-2A>T Likely pathogenic ★★ same type
TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same type
TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same type
TTN c.107224-1G>C Pathogenic/Likely pathogenic ★★ 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/ttn-p-arg26331gln (accessed [today's date]).

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