Is COL6A3 p.Phe1852Ser (c.5555T>C) pathogenic?

COL6A3 p.Phe1852Ser (c.5555T>C) is classified Conflicting classifications of pathogenicity in COL6A3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-25). AlphaMissense: likely pathogenic (0.8705); Rare (popmax 0.181%, sas); Associated with Inborn genetic diseases.

What condition is associated with COL6A3 p.Phe1852Ser (c.5555T>C)?

COL6A3 p.Phe1852Ser (c.5555T>C) is associated with Inborn genetic diseases, Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Phe1852Ser (c.5555T>C) in the general population?

COL6A3 p.Phe1852Ser (c.5555T>C) is rare (popmax 0.181%, sas) (gnomAD).

What do computational predictors say about COL6A3 p.Phe1852Ser (c.5555T>C)?

AlphaMissense predicts likely pathogenic (score 0.8705) — an in-silico prediction, not a clinical call.

COL6A3 p.Phe1852Ser

c.5555T>C · rs148488423 · VCV498581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8705 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, sas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8705	likely pathogenic
REVEL	0.835	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,991 bp · p 0.73 · regional, not allelic
Overall
CADD	24.8	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 0.181% South Asian · 165/91,086 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.0113% 182/1,614,038 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.181%	552
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-American	0.00266%	37,527
European (non-Finnish)	0.000847%	118,003

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: COL6A3
Protein: p.Phe1852Ser
Coding: c.5555T>C
MANE Select: NM_004369
dbSNP: rs148488423
Type: single nucleotide variant
Location: chr2:237365981 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1852: the vwfa 10 domain; the 'nonhelical region' region

Full COL6A3 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

Also linked: Bethlem myopathy 1A

Similar variants

COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+1G>A Pathogenic ★★ same condition
COL6A3 c.6157-2A>C Pathogenic ★★ same condition
COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>A Pathogenic ★★ same condition
COL6A3 c.6309+1G>A Pathogenic ★★ same condition
COL6A3 c.6309+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6310-2A>G 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/col6a3-p-phe1852ser (accessed [today's date]).

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