Is COL28A1 p.Pro83Ser (c.247C>T) pathogenic?

COL28A1 p.Pro83Ser (c.247C>T) is classified Uncertain significance in COL28A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0973); Ultra-rare (popmax 0.0134%, afr).

How common is COL28A1 p.Pro83Ser (c.247C>T) in the general population?

COL28A1 p.Pro83Ser (c.247C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about COL28A1 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

COL28A1 p.Pro83Ser

c.247C>T · VCV4232194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -6.41	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 3.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 174 kb · p 8.4e-10 · regional, not allelic
Overall
CADD	16.31	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

Grpmax group 0.0134% African / African-American · 10/74,798 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00551%

Overall 0.000686% 11/1,604,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.00161%	62,154

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: COL28A1
Protein: p.Pro83Ser
Coding: c.247C>T
MANE Select: NM_001037763
Type: single nucleotide variant
Location: chr7:7531782 (GRCh38)
Gene constraint: LOEUF 1.124 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.81
Residue 83: the vwfa 1 domain

Full COL28A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL28A1 c.1792-2A>G Uncertain significance ★ same type
COL28A1 p.Ala1075Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala274Thr Uncertain significance ★ ⚠ same type
COL28A1 p.Ala535Gly Uncertain significance ★ ⚠ same type
COL28A1 p.Ala631Asp Uncertain significance ★ ⚠ same type
COL28A1 p.Ala825Val Uncertain significance ★ ⚠ same type
COL28A1 p.Ala864Ser Uncertain significance ★ ⚠ same type
COL28A1 p.Arg1087Gln Uncertain significance ★ ⚠ 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/col28a1-p-pro83ser (accessed [today's date]).

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