Is COL14A1 p.Val808Met (c.2422G>A) pathogenic?

COL14A1 p.Val808Met (c.2422G>A) is classified Uncertain significance in COL14A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely pathogenic (0.662); Ultra-rare (popmax 0.0534%, afr).

How common is COL14A1 p.Val808Met (c.2422G>A) in the general population?

COL14A1 p.Val808Met (c.2422G>A) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

What do computational predictors say about COL14A1 p.Val808Met (c.2422G>A)?

AlphaMissense predicts likely pathogenic (score 0.662) — an in-silico prediction, not a clinical call.

COL14A1 p.Val808Met

c.2422G>A · VCV3495090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.662 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.662	likely pathogenic
REVEL	0.563	indeterminate
SaProt	LLR -11.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 174 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0534% African / African-American · 40/74,970 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00279% 45/1,613,630 alleles · ultra-rare exomes 18/1,461,434 · genomes 27/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,874
Remaining individualsnot grpmax-eligible	0.0064%	15,618
Admixed American	0.00167%	60,012

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: COL14A1
Protein: p.Val808Met
Coding: c.2422G>A
MANE Select: NM_021110
Type: single nucleotide variant
Location: chr8:120243951 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06
Residue 808: the fibronectin type-iii 6 domain

Full COL14A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL14A1 p.Val808Ala Uncertain significance ★ ⚠ same residue
COL14A1 p.Thr687Met Uncertain significance ★★ ⚠ same type
COL14A1 c.1192-76G>A Benign ★★ same type
COL14A1 c.1322-124C>G Benign ★★ same type
COL14A1 c.2138-137G>A Benign ★★ same type
COL14A1 c.2349+209C>T Benign ★★ same type
COL14A1 c.2349+232G>T Benign ★★ same type
COL14A1 c.2480-9T>C Benign ★★ 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/col14a1-p-val808met (accessed [today's date]).

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