Is TTC19 p.Asp90Glu (c.270C>G) pathogenic?

TTC19 p.Asp90Glu (c.270C>G) is classified Uncertain significance in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0451%, mid); Associated with mitochondrial complex III deficiency nuclear type 2.

What condition is associated with TTC19 p.Asp90Glu (c.270C>G)?

TTC19 p.Asp90Glu (c.270C>G) is associated with mitochondrial complex III deficiency nuclear type 2 (ClinVar).

How common is TTC19 p.Asp90Glu (c.270C>G) in the general population?

TTC19 p.Asp90Glu (c.270C>G) is ultra-rare (popmax 0.0451%, mid) (gnomAD).

What do computational predictors say about TTC19 p.Asp90Glu (c.270C>G)?

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

TTC19 p.Asp90Glu

c.270C>G · rs757875189 · VCV321943

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 0.0451%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial complex III deficiency nuclear type 2

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -3.19	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 -0.23	GERP -1.3, phastCons 0.11
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.9 · regional, not allelic
Overall
CADD	15.16	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 0.0451% Middle Eastern · 2/4,434 alleles

Filtering AF 0.00799% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00325%

Overall 0.000439% 7/1,594,502 alleles · ultra-rare exomes 5/1,442,206 · genomes 2/152,296 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0451%	2,217
East Asian	0.00892%	11,206
South Asian	0.0011%	90,812

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.Asp90Glu
Coding: c.270C>G
MANE Select: NM_017775
dbSNP: rs757875189
Type: single nucleotide variant
Location: chr17:16000203 (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

mitochondrial complex III deficiency nuclear type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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.Ala263Ser Uncertain significance ★★ ⚠ same condition
TTC19 p.Arg102Gly 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-asp90glu (accessed [today's date]).

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