Is TTC19 p.Ala263Ser (c.787G>T) pathogenic?

TTC19 p.Ala263Ser (c.787G>T) is classified Uncertain significance in TTC19 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.2111); Ultra-rare (popmax 0.0857%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TTC19 p.Ala263Ser (c.787G>T)?

TTC19 p.Ala263Ser (c.787G>T) is associated with Inborn genetic diseases, mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Ala263Ser (c.787G>T) in the general population?

TTC19 p.Ala263Ser (c.787G>T) is ultra-rare (popmax 0.0857%, nfe) (gnomAD).

What do computational predictors say about TTC19 p.Ala263Ser (c.787G>T)?

AlphaMissense predicts likely benign (score 0.2111) — an in-silico prediction, not a clinical call.

TTC19 p.Ala263Ser

c.787G>T · rs141892030 · VCV215302

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0857%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2111	likely benign
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -8.54	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	27.5	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 0.0857% European (non-Finnish) · 1,011/1,179,922 alleles

Filtering AF 0.0812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.0661% 1,067/1,613,876 alleles · ultra-rare exomes 1,013/1,461,692 · genomes 54/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0857%	1,167
Remaining individualsnot grpmax-eligible	0.0592%	1,688
Finnishnot grpmax-eligible	0.0125%	8,002
African / African-American	0.012%	8,323
Admixed American	0.00167%	59,990
South Asian	0.0011%	91,084

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.Ala263Ser
Coding: c.787G>T
MANE Select: NM_017775
dbSNP: rs141892030
Type: single nucleotide variant
Location: chr17:16025127 (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

Also linked: mitochondrial complex III deficiency nuclear type 2

Similar variants

TTC19 p.Ala263= Likely benign ★ same residue
TTC19 p.Gln195Ter Pathogenic/Likely pathogenic ★★ same condition
TTC19 p.Leu185Pro Pathogenic/Likely pathogenic ★★ same condition
TTC19 p.Leu219Ter Pathogenic ★★ same condition
TTC19 c.581+4A>C Uncertain significance ★★ same condition
TTC19 c.994+3A>T Uncertain significance ★★ same condition
TTC19 p.Ala122Thr Uncertain significance ★★ ⚠ same condition
TTC19 p.Ala200Val 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-ala263ser (accessed [today's date]).

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