Is TTC19 p.Ser267Phe (c.800C>T) pathogenic?

TTC19 p.Ser267Phe (c.800C>T) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-28). AlphaMissense: likely pathogenic (0.7545); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Ser267Phe (c.800C>T)?

TTC19 p.Ser267Phe (c.800C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Ser267Phe (c.800C>T) in the general population?

TTC19 p.Ser267Phe (c.800C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTC19 p.Ser267Phe (c.800C>T)?

AlphaMissense predicts likely pathogenic (score 0.7545) — an in-silico prediction, not a clinical call.

TTC19 p.Ser267Phe

c.800C>T · rs2549951421 · VCV2286563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7545 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7545	likely pathogenic
REVEL	0.47	indeterminate
SaProt	LLR -10.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	25.4	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: TTC19
Protein: p.Ser267Phe
Coding: c.800C>T
MANE Select: NM_017775
dbSNP: rs2549951421
Type: single nucleotide variant
Location: chr17:16025140 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.28

Full TTC19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTC19 p.Ala200Val Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala85Val Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg102Gly Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg124His Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg294Cys Uncertain significance ★★ ⚠ same condition
TTC19 p.Ile206Met Uncertain significance ★★ ⚠ same condition
TTC19 p.Lys160Gln Uncertain significance ★★ ⚠ 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/ttc19-p-ser267phe (accessed [today's date]).

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