Is COL8A2 p.Arg372Cys (c.1114C>T) pathogenic?

COL8A2 p.Arg372Cys (c.1114C>T) is classified Uncertain significance in COL8A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-08). AlphaMissense: likely benign (0.1787); Very rare (popmax 0.0045%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL8A2 p.Arg372Cys (c.1114C>T)?

COL8A2 p.Arg372Cys (c.1114C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL8A2 p.Arg372Cys (c.1114C>T) in the general population?

COL8A2 p.Arg372Cys (c.1114C>T) is very rare (popmax 0.0045%, eas) (gnomAD).

What do computational predictors say about COL8A2 p.Arg372Cys (c.1114C>T)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

COL8A2 p.Arg372Cys

c.1114C>T · rs780318859 · VCV2269162

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0045%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.475	indeterminate
SaProt	LLR -9.98	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 9.8	GERP -0.24, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,954 bp · p 0.078 · regional, not allelic
Overall
CADD	24.6	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 0.0045% East Asian · 2/44,418 alleles

Filtering AF 0.00343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00373% 60/1,606,716 alleles · very rare exomes 54/1,454,768 · genomes 6/151,948 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0045%	22,209
European (non-Finnish)	0.00442%	22,643
South Asian	0.00333%	30,009
African / African-American	0.00268%	37,313
Remaining individualsnot grpmax-eligible	0.00161%	62,178

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.Arg372Cys
Coding: c.1114C>T
MANE Select: NM_005202
dbSNP: rs780318859
Type: single nucleotide variant
Location: chr1:36098567 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 372: 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.Arg149Gln Uncertain significance ★★ ⚠ same condition
COL8A2 p.Arg263Ser 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
COL8A2 p.Gly601Ala Uncertain significance ★★ ⚠ same condition
COL8A2 p.Lys426Gln 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-arg372cys (accessed [today's date]).

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