Is COL4A6 p.Pro95Ser (c.283C>T) pathogenic?

COL4A6 p.Pro95Ser (c.283C>T) is classified Uncertain significance in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely benign (0.0972); Ultra-rare (popmax 0.0231%, mid).

How common is COL4A6 p.Pro95Ser (c.283C>T) in the general population?

COL4A6 p.Pro95Ser (c.283C>T) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

What do computational predictors say about COL4A6 p.Pro95Ser (c.283C>T)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

COL4A6 p.Pro95Ser

c.283C>T · rs928894320 · VCV2992151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -5.10	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 6.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 281 kb · p 0.15 · regional, not allelic
Overall
CADD	17.03	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P96S vs ClinVar P95S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% Middle Eastern · 1/4,332 alleles

Filtering AF 0.000165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00055% 6/1,091,697 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,332
European (non-Finnish)	0.000562%	177,980

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: COL4A6
Protein: p.Pro95Ser
Coding: c.283C>T
MANE Select: NM_033641
dbSNP: rs928894320
Type: single nucleotide variant
Location: chrX:108219739 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 95: the 'triple-helical region' region

Full COL4A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A6 p.Pro95Ala Uncertain significance ★ ⚠ same residue
COL4A6 p.Pro95Leu Uncertain significance ★ ⚠ same residue
COL4A6 c.3970+5G>A Uncertain significance ★★ same type
COL4A6 p.Ala1275Thr Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala398Ser Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala421Gly Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala748Val Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala886Thr 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/col4a6-p-pro95ser (accessed [today's date]).

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