Is TTC19 p.Arg294Cys (c.880C>T) pathogenic?

TTC19 p.Arg294Cys (c.880C>T) is classified Uncertain significance in TTC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-12). AlphaMissense: likely benign (0.0838); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Arg294Cys (c.880C>T)?

TTC19 p.Arg294Cys (c.880C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Arg294Cys (c.880C>T) in the general population?

TTC19 p.Arg294Cys (c.880C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about TTC19 p.Arg294Cys (c.880C>T)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

TTC19 p.Arg294Cys

c.880C>T · rs370754599 · VCV1905792

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.52	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.7, phastCons 0.96
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.015% Admixed American · 9/59,990 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00242% 39/1,613,992 alleles · ultra-rare exomes 33/1,461,850 · genomes 6/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
Finnishnot grpmax-eligible	0.00937%	10,672
South Asian	0.00329%	30,354
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00153%	65,556
African / African-American	0.00133%	74,930

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: TTC19
Protein: p.Arg294Cys
Coding: c.880C>T
MANE Select: NM_017775
dbSNP: rs370754599
Type: single nucleotide variant
Location: chr17:16026588 (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.Arg294His Likely benign ★ 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.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-arg294cys (accessed [today's date]).

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