Is TTC19 c.462+247T>C pathogenic?

TTC19 c.462+247T>C is classified Benign in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-14). Common (popmax 55.9%, mid) — too common for a highly-penetrant pathogenic allele.

TTC19 c.462+247T>C

Q: How common is TTC19 c.462+247T>C in the general population?

TTC19 c.462+247T>C is common (popmax 55.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11078321 · VCV667504

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 55.9%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +247	deep intronic (+247 nt into the intron)
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.53	GERP -0.89
Non-coding constraint	Z 0.84	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	7.724	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.9% Middle Eastern · 161/288 alleles

Filtering AF 52.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.5%

Overall 42.6% 64,620/151,766 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	63.8%	2
Finnishnot grpmax-eligible	56%	2
Middle Easterngrpmax	55.9%	2
European (non-Finnish)	53.2%	2
Amishnot grpmax-eligible	52.1%	2
Remaining individualsnot grpmax-eligible	45.7%	2
Admixed American	44.7%	2
South Asian	37%	3
African / African-American	23%	4
East Asian	14.4%	7

Ashkenazi Jewish 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
Coding: c.462+247T>C
MANE Select: NM_017775
dbSNP: rs11078321
Type: single nucleotide variant
Location: chr17:16003078 (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-c-462-plus-247t-c (accessed [today's date]).

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