Is COL8A2 p.Leu8= (c.22C>T) pathogenic?

COL8A2 p.Leu8= (c.22C>T) is classified Benign in COL8A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-13). Low-frequency (popmax 1.71%, eas).

How common is COL8A2 p.Leu8= (c.22C>T) in the general population?

COL8A2 p.Leu8= (c.22C>T) is low-frequency (popmax 1.71%, eas) (gnomAD).

COL8A2 p.Leu8=

c.22C>T · rs75750458 · VCV2059234

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.71%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP 0.27, phastCons 0.88
Overall
CADD	4.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.71% East Asian · 736/42,976 alleles

Filtering AF 1.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.168% 2,652/1,575,346 alleles · low-frequency exomes 2,264/1,423,022 · genomes 388/152,324 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.07%	48
East Asiangrpmax	1.71%	58
Remaining individualsnot grpmax-eligible	0.234%	427
Ashkenazi Jewishnot grpmax-eligible	0.18%	557
South Asian	0.101%	994
European (non-Finnish)	0.037%	2,702
Middle Eastern	0.0166%	6,016
Admixed American	0.00925%	10,810
African / African-American	0.00538%	18,574

Finnish 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.Leu8=
Coding: c.22C>T
MANE Select: NM_005202
dbSNP: rs75750458
Type: single nucleotide variant
Location: chr1:36100221 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03

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

Similar variants

COL8A2 p.Leu8Gln Uncertain significance ★ ⚠ same residue
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

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-leu8 (accessed [today's date]).

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