Is TTC19 p.Phe204Ser (c.611T>C) pathogenic?

TTC19 p.Phe204Ser (c.611T>C) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely pathogenic (0.9866); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Phe204Ser (c.611T>C)?

TTC19 p.Phe204Ser (c.611T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Phe204Ser (c.611T>C) in the general population?

TTC19 p.Phe204Ser (c.611T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTC19 p.Phe204Ser (c.611T>C)?

AlphaMissense predicts likely pathogenic (score 0.9866) — an in-silico prediction, not a clinical call.

TTC19 p.Phe204Ser

c.611T>C · VCV3975252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9866 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9866	likely pathogenic · top 1% in TTC19
REVEL	0.547	indeterminate
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

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.Phe204Ser
Coding: c.611T>C
MANE Select: NM_017775
Type: single nucleotide variant
Location: chr17:16006503 (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.Phe204Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-phe204ser (accessed [today's date]).

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