Is COL5A3 p.Pro625Ser (c.1873C>T) pathogenic?

COL5A3 p.Pro625Ser (c.1873C>T) is classified Uncertain significance in COL5A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1031); Ultra-rare (popmax 0.0165%, mid).

How common is COL5A3 p.Pro625Ser (c.1873C>T) in the general population?

COL5A3 p.Pro625Ser (c.1873C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about COL5A3 p.Pro625Ser (c.1873C>T)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

COL5A3 p.Pro625Ser

c.1873C>T · rs1480951251 · VCV3147645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -8.96	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 6.4	GERP 2.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	20.2	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000186% 3/1,613,800 alleles · ultra-rare exomes 1/1,461,676 · genomes 2/152,124 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,250

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: COL5A3
Protein: p.Pro625Ser
Coding: c.1873C>T
MANE Select: NM_015719
dbSNP: rs1480951251
Type: single nucleotide variant
Location: chr19:9992024 (GRCh38)
Gene constraint: LOEUF 0.812 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.26
Residue 625: the 'triple-helical region' region; the 'disordered' region

Full COL5A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL5A3 p.Arg1177Trp Uncertain significance ★★ ⚠ same type
COL5A3 p.Asp855= Benign ★★ same type
COL5A3 p.Phe178= Benign ★★ same type
COL5A3 p.Pro1050Ser Benign ★★ same type
COL5A3 p.Pro496= Likely benign ★★ same type
COL5A3 p.Val1195Ala Benign ★★ same type
COL5A3 p.Ala1005Thr Uncertain significance ★ ⚠ same type
COL5A3 p.Ala1096Thr 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/col5a3-p-pro625ser (accessed [today's date]).

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