Is TTC5 p.Lys115Gln (c.343A>C) pathogenic?

TTC5 p.Lys115Gln (c.343A>C) is classified Uncertain significance in TTC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.5881); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism.

How common is TTC5 p.Lys115Gln (c.343A>C) in the general population?

TTC5 p.Lys115Gln (c.343A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTC5 p.Lys115Gln (c.343A>C)?

AlphaMissense predicts likely pathogenic (score 0.5881) — an in-silico prediction, not a clinical call.

TTC5 p.Lys115Gln

Q: What condition is associated with TTC5 p.Lys115Gln (c.343A>C)?

TTC5 p.Lys115Gln (c.343A>C) is associated with neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism (ClinVar).

c.343A>C · rs1482085635 · VCV3065695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism

Computational evidence

Protein change
AlphaMissense	0.5881	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -11.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.29 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTC5
Protein: p.Lys115Gln
Coding: c.343A>C
MANE Select: NM_138376
dbSNP: rs1482085635
Type: single nucleotide variant
Location: chr14:20300660 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.54 · 4 PDB
Residue 115: an α-helix

Full TTC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTC5 p.Arg27Ter Likely pathogenic ★★ same condition
TTC5 p.Arg395Ter Uncertain significance ★ same condition
TTC5 p.Arg409Ter Conflicting classifications of pathogenicity ★ same condition
TTC5 p.Gln140Ter Uncertain significance ★ same condition
TTC5 p.Gln148Ter Uncertain significance ★ same condition
TTC5 p.Pro11Leu Uncertain significance ★ ⚠ same condition
TTC5 c.51+1G>A Pathogenic same condition
TTC5 p.Ala231Val 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/ttc5-p-lys115gln (accessed [today's date]).

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