Is COA8 p.Trp55Arg (c.163T>C) pathogenic?

COA8 p.Trp55Arg (c.163T>C) is classified Uncertain significance in COA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely pathogenic (0.9828); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COA8 p.Trp55Arg (c.163T>C)?

COA8 p.Trp55Arg (c.163T>C) is associated with Inborn genetic diseases (ClinVar).

How common is COA8 p.Trp55Arg (c.163T>C) in the general population?

COA8 p.Trp55Arg (c.163T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about COA8 p.Trp55Arg (c.163T>C)?

AlphaMissense predicts likely pathogenic (score 0.9828) — an in-silico prediction, not a clinical call.

COA8 p.Trp55Arg

c.163T>C · rs138791247 · VCV3146995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9828	likely pathogenic · top 2% in COA8
REVEL	0.453	indeterminate
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.52, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 27 kb · p 0.018 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W68R vs ClinVar W55R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,046 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,140 alleles · very rare

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: COA8
Protein: p.Trp55Arg
Coding: c.163T>C
MANE Select: NM_001370595
dbSNP: rs138791247
Type: single nucleotide variant
Location: chr14:103571662 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.19

Full COA8 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

Similar variants

COA8 c.-32C>G Uncertain significance ★★ ⚠ same condition
COA8 p.Ala140Val Uncertain significance ★★ ⚠ same condition
COA8 p.Ala27Val Uncertain significance ★★ ⚠ same condition
COA8 p.Arg164Cys Uncertain significance ★★ ⚠ same condition
COA8 p.Asn135Ser Uncertain significance ★★ ⚠ same condition
COA8 p.Asn165Ser Uncertain significance ★★ ⚠ same condition
COA8 p.Gln88Arg Uncertain significance ★★ ⚠ same condition
COA8 p.Glu137Gln 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/coa8-p-trp55arg (accessed [today's date]).

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