Is COL10A1 p.Phe554Leu (c.1662T>A) pathogenic?

COL10A1 p.Phe554Leu (c.1662T>A) is classified Likely pathogenic in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.9733); Absent from gnomAD v4.1; Associated with COL10A1-related disorder.

What condition is associated with COL10A1 p.Phe554Leu (c.1662T>A)?

COL10A1 p.Phe554Leu (c.1662T>A) is associated with COL10A1-related disorder (ClinVar).

How common is COL10A1 p.Phe554Leu (c.1662T>A) in the general population?

COL10A1 p.Phe554Leu (c.1662T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL10A1 p.Phe554Leu (c.1662T>A)?

AlphaMissense predicts likely pathogenic (score 0.9733) — an in-silico prediction, not a clinical call.

COL10A1 p.Phe554Leu

c.1662T>A · rs2534085175 · VCV2629714

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9733 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COL10A1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9733	likely pathogenic ✓ concordant with ClinVar · top 1% in COL10A1
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -3.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	21.6	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: COL10A1
Protein: p.Phe554Leu
Coding: c.1662T>A
MANE Select: NM_000493
dbSNP: rs2534085175
Type: single nucleotide variant
Location: chr6:116120454 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 554: the c1q domain; a β-strand; the 'nonhelical region (nc1)' region

Full COL10A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL10A1-related disorder

Similar variants

COL10A1 p.Cys591Arg Likely pathogenic ★★ same condition
COL10A1 p.Gly18Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL10A1 p.Thr280Arg Uncertain significance ★★ ⚠ same condition
COL10A1 p.Gln635Ter Likely pathogenic ★ same condition
COL10A1 p.Gly674Arg Pathogenic ★ same condition
COL10A1 p.Leu614Gln Likely pathogenic ★ same condition
COL10A1 p.Ser673Pro Likely pathogenic ★ same condition
COL10A1 p.Tyr632Ter Pathogenic ★ 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/col10a1-p-phe554leu (accessed [today's date]).

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