Is COL8A2 p.Ala554= (c.1662C>T) pathogenic?

COL8A2 p.Ala554= (c.1662C>T) is classified Likely benign in COL8A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-03). Ultra-rare (popmax 0.0168%, mid); Associated with COL8A2-related disorder.

What condition is associated with COL8A2 p.Ala554= (c.1662C>T)?

COL8A2 p.Ala554= (c.1662C>T) is associated with COL8A2-related disorder (ClinVar).

How common is COL8A2 p.Ala554= (c.1662C>T) in the general population?

COL8A2 p.Ala554= (c.1662C>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

COL8A2 p.Ala554=

c.1662C>T · rs753604558 · VCV3037037

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

COL8A2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -4.2
Overall
CADD	0.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,960 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00376% 60/1,594,904 alleles · ultra-rare exomes 47/1,442,802 · genomes 13/152,102 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,960
African / African-American	0.00936%	10,684
European (non-Finnish)	0.00417%	23,983
Remaining individualsnot grpmax-eligible	0.00323%	30,932
Admixed American	0.00169%	59,040

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.Ala554=
Coding: c.1662C>T
MANE Select: NM_005202
dbSNP: rs753604558
Type: single nucleotide variant
Location: chr1:36098019 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 554: the 'nonhelical region (nc1)' region

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

Disease context

COL8A2-related disorder

Similar variants

COL8A2 p.Ala554Thr Uncertain significance ★ ⚠ same residue
COL8A2 p.Ala554Val Uncertain significance ★ ⚠ same residue
COL8A2 p.Leu450Trp Pathogenic ★ ⚠ same condition
COL8A2 c.*3C>T Likely benign same condition
COL8A2 p.Gly357Arg Likely benign same condition
COL8A2 p.Gly95fs Uncertain significance ★ same condition
COL8A2 p.Arg149Gln Uncertain significance ★★ ⚠ same type
COL8A2 p.Arg263Ser 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-ala554 (accessed [today's date]).

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