Is COL8A2 p.Arg155Trp (c.463C>T) pathogenic?

COL8A2 p.Arg155Trp (c.463C>T) is classified Uncertain significance in COL8A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1918); Very rare (popmax 0.00619%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL8A2 p.Arg155Trp (c.463C>T)?

COL8A2 p.Arg155Trp (c.463C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL8A2 p.Arg155Trp (c.463C>T) in the general population?

COL8A2 p.Arg155Trp (c.463C>T) is very rare (popmax 0.00619%, amr) (gnomAD).

What do computational predictors say about COL8A2 p.Arg155Trp (c.463C>T)?

AlphaMissense predicts likely benign (score 0.1918) — an in-silico prediction, not a clinical call.

COL8A2 p.Arg155Trp

c.463C>T · VCV3495808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00619%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1918	likely benign
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -11.00	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,954 bp · p 0.078 · regional, not allelic
Overall
CADD	21.8	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 0.00619% Admixed American · 3/48,494 alleles

Filtering AF 0.00354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0032%

Overall 0.00397% 61/1,537,860 alleles · very rare exomes 58/1,386,098 · genomes 3/151,762 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00619%	16,165
Remaining individualsnot grpmax-eligible	0.00506%	19,747
European (non-Finnish)	0.00456%	21,947
Ashkenazi Jewishnot grpmax-eligible	0.00359%	27,886
East Asian	0.00245%	40,762
Finnishnot grpmax-eligible	0.00172%	58,114

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: COL8A2
Protein: p.Arg155Trp
Coding: c.463C>T
MANE Select: NM_005202
Type: single nucleotide variant
Location: chr1:36099218 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 155: a UniProt-annotated variant site (in); the 'disordered' region; the 'triple-helical region' region

Full COL8A2 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

COL8A2 p.Arg155Gln Benign ★★ same residue
COL8A2 p.Arg149Gln Uncertain significance ★★ ⚠ same condition
COL8A2 p.Arg263Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Arg372Cys Uncertain significance ★★ ⚠ same condition
COL8A2 p.Glu568Lys Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly549Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly550Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly559Glu 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/col8a2-p-arg155trp (accessed [today's date]).

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