Is COL8A2 p.Ser679Ala (c.2035T>G) pathogenic?

COL8A2 p.Ser679Ala (c.2035T>G) is classified Uncertain significance in COL8A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.5643); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL8A2 p.Ser679Ala (c.2035T>G)?

COL8A2 p.Ser679Ala (c.2035T>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL8A2 p.Ser679Ala (c.2035T>G) in the general population?

COL8A2 p.Ser679Ala (c.2035T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL8A2 p.Ser679Ala (c.2035T>G)?

AlphaMissense predicts likely pathogenic (score 0.5643) — an in-silico prediction, not a clinical call.

COL8A2 p.Ser679Ala

c.2035T>G · VCV4616331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5643 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5643	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 648 bp · p 0.0003 · regional, not allelic
Overall
CADD	27.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL8A2
Protein: p.Ser679Ala
Coding: c.2035T>G
MANE Select: NM_005202
Type: single nucleotide variant
Location: chr1:36097646 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 679: the c1q domain; the 'nonhelical region (nc1)' 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.Ser679Leu Uncertain significance ★ ⚠ 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-ser679ala (accessed [today's date]).

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