Is COL27A1 p.Pro705Ser (c.2113C>T) pathogenic?

COL27A1 p.Pro705Ser (c.2113C>T) is classified Benign/Likely benign in COL27A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-08). AlphaMissense: likely benign (0.0792); Rare (popmax 0.6%, eas); Associated with Steel syndrome.

What condition is associated with COL27A1 p.Pro705Ser (c.2113C>T)?

COL27A1 p.Pro705Ser (c.2113C>T) is associated with Steel syndrome (ClinVar).

How common is COL27A1 p.Pro705Ser (c.2113C>T) in the general population?

COL27A1 p.Pro705Ser (c.2113C>T) is rare (popmax 0.6%, eas) (gnomAD).

How is Steel syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COL27A1 p.Pro705Ser (c.2113C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

COL27A1 p.Pro705Ser

c.2113C>T · rs139039113 · VCV716538

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.6%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Steel syndrome

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP 2
Regional constraint	o/e 1.03	unconstrained · MANE · 76 kb · p 0.25 · regional, not allelic
Overall
CADD	13.77	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

Grpmax group 0.6% East Asian · 269/44,864 alleles

Filtering AF 0.541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.518%

Overall 0.0218% 352/1,614,096 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.6%	167
Remaining individualsnot grpmax-eligible	0.115%	868
Admixed American	0.01%	10,005
European (non-Finnish)	0.000424%	235,994

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: COL27A1
Protein: p.Pro705Ser
Coding: c.2113C>T
MANE Select: NM_032888
dbSNP: rs139039113
Type: single nucleotide variant
Location: chr9:114196001 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.13
Residue 705: the 'triple-helical region' region; the 'disordered' region; the collagen-like 2 domain

Full COL27A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Steel syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Steel syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COL27A1 p.Pro705= Benign ★★ same residue
COL27A1 p.Pro705Leu Uncertain significance ★ ⚠ same residue
COL27A1 c.62+1G>T Likely pathogenic ★★ same condition
COL27A1 p.Arg1354Ter Pathogenic ★★ same condition
COL27A1 p.Arg707Ter Pathogenic ★★ same condition
COL27A1 p.Arg774Ter Pathogenic/Likely pathogenic ★★ same condition
COL27A1 p.Gln406Ter Pathogenic/Likely pathogenic ★★ same condition
COL27A1 p.Gly1147Ter Pathogenic/Likely 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/col27a1-p-pro705ser (accessed [today's date]).

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