Is TTN p.Asn8317Lys (c.24951C>G) pathogenic?

TTN p.Asn8317Lys (c.24951C>G) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.5894); Ultra-rare (popmax 0.0214%, afr).

How common is TTN p.Asn8317Lys (c.24951C>G) in the general population?

TTN p.Asn8317Lys (c.24951C>G) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about TTN p.Asn8317Lys (c.24951C>G)?

AlphaMissense predicts likely pathogenic (score 0.5894) — an in-silico prediction, not a clinical call.

TTN p.Asn8317Lys

c.24951C>G · rs370154022 · VCV3234684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5894 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Computational evidence

Protein change
AlphaMissense	0.5894	likely pathogenic
REVEL	0.374	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -5.6
Regional constraint	o/e 0.99	unconstrained · MANE · 141 kb · p 0.23 · regional, not allelic
Overall
CADD	0.042	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 N8000K vs ClinVar N8317K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,886 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00112% 18/1,613,588 alleles · ultra-rare exomes 6/1,461,474 · genomes 12/152,114 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,680
European (non-Finnish)	0.00017%	589,859

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.Asn8317Lys
Coding: c.24951C>G
MANE Select: NM_001267550
dbSNP: rs370154022
Type: single nucleotide variant
Location: chr2:178718055 (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.Asn8317= Conflicting classifications of pathogenicity ★ same residue
TTN p.Asn8317Ile Uncertain significance ★ 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-asn8317lys (accessed [today's date]).

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