Is TTC19 p.Ala242Thr (c.724G>A) pathogenic?

TTC19 p.Ala242Thr (c.724G>A) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0165%, mid).

How common is TTC19 p.Ala242Thr (c.724G>A) in the general population?

TTC19 p.Ala242Thr (c.724G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TTC19 p.Ala242Thr (c.724G>A)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

TTC19 p.Ala242Thr

c.724G>A · rs762239880 · VCV2415764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.556	indeterminate
SaProt	LLR -4.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -1.4, phastCons 0.008
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	13.54	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000991% 16/1,613,836 alleles · ultra-rare exomes 14/1,461,656 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
Admixed American	0.00333%	29,993
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,080
European (non-Finnish)	0.000932%	107,260

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.Ala242Thr
Coding: c.724G>A
MANE Select: NM_017775
dbSNP: rs762239880
Type: single nucleotide variant
Location: chr17:16025064 (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 p.Ala242= Likely benign ★ same residue
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

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-ala242thr (accessed [today's date]).

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