Is COL11A1 p.Ser355Pro (c.1063T>C) pathogenic?

COL11A1 p.Ser355Pro (c.1063T>C) is classified Conflicting classifications of pathogenicity in COL11A1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.0729); Ultra-rare (popmax 0.0155%, nfe).

How common is COL11A1 p.Ser355Pro (c.1063T>C) in the general population?

COL11A1 p.Ser355Pro (c.1063T>C) is ultra-rare (popmax 0.0155%, nfe) (gnomAD).

What do computational predictors say about COL11A1 p.Ser355Pro (c.1063T>C)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

COL11A1 p.Ser355Pro

c.1063T>C · rs141036911 · VCV452469

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -6.28	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 2.1	GERP -3.3, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 230 kb · p 0.038 · regional, not allelic
Overall
CADD	16.38	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 0.0155% European (non-Finnish) · 183/1,179,838 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0121% 195/1,613,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0155%	6,447
Remaining individualsnot grpmax-eligible	0.0128%	7,812
African / African-American	0.004%	25,008
Admixed American	0.00167%	60,002

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: COL11A1
Protein: p.Ser355Pro
Coding: c.1063T>C
MANE Select: NM_001854
dbSNP: rs141036911
Type: single nucleotide variant
Location: chr1:103022924 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 355: the 'nonhelical region' region

Full COL11A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL11A1 p.Ser355Thr Uncertain significance ★ same residue
COL11A1 p.Ser355Ala Benign ★ same residue
COL11A1 c.1245+1G>A Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1245+1G>T Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1629+1G>A Likely pathogenic ★★ same type
COL11A1 c.1630-1G>T Pathogenic ★★ same type
COL11A1 c.1791+1G>T Likely pathogenic ★★ same type
COL11A1 c.1900-1G>A Likely pathogenic ★★ 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/col11a1-p-ser355pro (accessed [today's date]).

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