Is TTC19 p.Ile118Asn (c.353T>A) pathogenic?

TTC19 p.Ile118Asn (c.353T>A) is classified Uncertain significance in TTC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.5097); Very rare (popmax 0.00153%, nfe).

How common is TTC19 p.Ile118Asn (c.353T>A) in the general population?

TTC19 p.Ile118Asn (c.353T>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about TTC19 p.Ile118Asn (c.353T>A)?

AlphaMissense predicts ambiguous (score 0.5097) — an in-silico prediction, not a clinical call.

TTC19 p.Ile118Asn

c.353T>A · rs781360490 · VCV1487412

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5097	ambiguous
REVEL	0.507	indeterminate
SaProt	LLR -6.03	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	26.4	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

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,968 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,613,466 alleles · very rare exomes 21/1,461,262 · genomes 0/152,204 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,249
Finnishnot grpmax-eligible	0.00158%	63,452
European (non-Finnish)grpmax	0.00153%	65,554

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile118Asn
Coding: c.353T>A
MANE Select: NM_017775
dbSNP: rs781360490
Type: single nucleotide variant
Location: chr17:16001955 (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

Similar variants

TTC19 c.581+1G>C Pathogenic/Likely pathogenic ★★ same type
TTC19 p.Gln195Ter Pathogenic/Likely pathogenic ★★ same type
TTC19 p.Leu185Pro Pathogenic/Likely pathogenic ★★ same type
TTC19 p.Leu219Ter Pathogenic ★★ same type
TTC19 c.581+4A>C Uncertain significance ★★ same type
TTC19 c.994+3A>T Uncertain significance ★★ same type
TTC19 p.Ala122Thr Uncertain significance ★★ ⚠ same type
TTC19 p.Ala200Val Uncertain significance ★★ ⚠ same type

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-ile118asn (accessed [today's date]).

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