Is TTC19 p.Gln98His (c.294G>C) pathogenic?

TTC19 p.Gln98His (c.294G>C) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.1362); Ultra-rare (popmax 0.0231%, sas); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Gln98His (c.294G>C)?

TTC19 p.Gln98His (c.294G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TTC19 p.Gln98His (c.294G>C) in the general population?

TTC19 p.Gln98His (c.294G>C) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about TTC19 p.Gln98His (c.294G>C)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

TTC19 p.Gln98His

c.294G>C · rs557654875 · VCV2242559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.84, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	21.0	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 0.0231% South Asian · 21/90,916 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00138% 22/1,595,356 alleles · ultra-rare exomes 21/1,442,994 · genomes 1/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,329
Remaining individualsnot grpmax-eligible	0.00161%	62,088

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.Gln98His
Coding: c.294G>C
MANE Select: NM_017775
dbSNP: rs557654875
Type: single nucleotide variant
Location: chr17:16000227 (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.Gln98= 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.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-gln98his (accessed [today's date]).

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