Is COL8A2 p.Arg121Trp (c.361C>T) pathogenic?

COL8A2 p.Arg121Trp (c.361C>T) is classified Benign/Likely benign in COL8A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-08). AlphaMissense: likely benign (0.2077); Rare (popmax 0.257%, eas).

How common is COL8A2 p.Arg121Trp (c.361C>T) in the general population?

COL8A2 p.Arg121Trp (c.361C>T) is rare (popmax 0.257%, eas) (gnomAD).

What do computational predictors say about COL8A2 p.Arg121Trp (c.361C>T)?

AlphaMissense predicts likely benign (score 0.2077) — an in-silico prediction, not a clinical call.

COL8A2 p.Arg121Trp

c.361C>T · VCV3720707

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.257%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2077	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -8.57	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 1.8	GERP -3.6, phastCons 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 1,954 bp · p 0.078 · regional, not allelic
Overall
CADD	22.8	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 0.257% East Asian · 112/43,646 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.0205% 324/1,581,526 alleles · rare exomes 284/1,429,854 · genomes 40/151,672 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.518%	193
East Asiangrpmax	0.257%	390
Remaining individualsnot grpmax-eligible	0.0294%	3,400
European (non-Finnish)	0.00352%	28,438
South Asian	0.00345%	28,953
Finnishnot grpmax-eligible	0.0017%	58,844

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg121Trp
Coding: c.361C>T
MANE Select: NM_005202
Type: single nucleotide variant
Location: chr1:36099320 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 121: the 'disordered' region; the 'triple-helical region' region

Full COL8A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL8A2 p.Arg149Gln Uncertain significance ★★ ⚠ same type
COL8A2 p.Arg263Ser Uncertain significance ★★ ⚠ same type
COL8A2 p.Arg372Cys Uncertain significance ★★ ⚠ same type
COL8A2 p.Glu568Lys Uncertain significance ★★ ⚠ same type
COL8A2 p.Gly549Ser Uncertain significance ★★ ⚠ same type
COL8A2 p.Gly550Ser Uncertain significance ★★ ⚠ same type
COL8A2 p.Gly559Glu Uncertain significance ★★ ⚠ same type
COL8A2 p.Gly601Ala Uncertain significance ★★ ⚠ same type

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-arg121trp (accessed [today's date]).

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