Is COL1A2 p.Val993Phe (c.2977G>T) pathogenic?

COL1A2 p.Val993Phe (c.2977G>T) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). AlphaMissense: likely benign (0.1012); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with COL1A2 p.Val993Phe (c.2977G>T)?

COL1A2 p.Val993Phe (c.2977G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is COL1A2 p.Val993Phe (c.2977G>T) in the general population?

COL1A2 p.Val993Phe (c.2977G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL1A2 p.Val993Phe (c.2977G>T)?

AlphaMissense predicts likely benign (score 0.1012) — an in-silico prediction, not a clinical call.

COL1A2 p.Val993Phe

c.2977G>T · VCV3268610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1012 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1012	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -1.1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	19.82	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

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: COL1A2
Protein: p.Val993Phe
Coding: c.2977G>T
MANE Select: NM_000089
Type: single nucleotide variant
Location: chr7:94426031 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 993: an α-helix; the 'disordered' region

Full COL1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A2 p.Val993Ile Uncertain significance ★ ⚠ same residue
COL1A2 p.Val993= Likely benign ★ same residue
COL1A2 p.Val993Leu Uncertain significance ★ ⚠ same residue
COL1A2 c.2565+1G>A Pathogenic ★★ same condition
COL1A2 p.Ala1119Thr Pathogenic/Likely pathogenic ★★ same condition
COL1A2 p.Gly259Ser Pathogenic/Likely pathogenic ★★ same condition
COL1A2 p.Gly907Ser Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1251+2T>G 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/col1a2-p-val993phe (accessed [today's date]).

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