Is ADAM19 p.Pro694Ser (c.2080C>T) pathogenic?

ADAM19 p.Pro694Ser (c.2080C>T) is classified Benign in ADAM19 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-13). AlphaMissense: likely benign (0.2216); Rare (popmax 0.393%, nfe).

How common is ADAM19 p.Pro694Ser (c.2080C>T) in the general population?

ADAM19 p.Pro694Ser (c.2080C>T) is rare (popmax 0.393%, nfe) (gnomAD).

What do computational predictors say about ADAM19 p.Pro694Ser (c.2080C>T)?

AlphaMissense predicts likely benign (score 0.2216) — an in-silico prediction, not a clinical call.

ADAM19 p.Pro694Ser

c.2080C>T · rs34882961 · VCV715897

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2216 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.393%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2216	likely benign
REVEL	0.681	pathogenic-leaning
SaProt	LLR -9.53	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.31 · regional, not allelic
Overall
CADD	31.0	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 0.393% European (non-Finnish) · 4,473/1,137,956 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.379%

Overall 0.351% 5,373/1,529,602 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.869%	115
European (non-Finnish)grpmax	0.393%	254
Ashkenazi Jewishnot grpmax-eligible	0.31%	323
Remaining individualsnot grpmax-eligible	0.294%	340
Admixed American	0.126%	792
African / African-American	0.0689%	1,452
Middle Eastern	0.0531%	1,884
South Asian	0.0169%	5,924

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADAM19
Protein: p.Pro694Ser
Coding: c.2080C>T
MANE Select: NM_033274
dbSNP: rs34882961
Type: single nucleotide variant
Location: chr5:157491630 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.93

Full ADAM19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM19 c.1130+67G>T Uncertain significance ★ same type
ADAM19 c.180+659A>C Uncertain significance ★ same type
ADAM19 c.251+324T>G Uncertain significance ★ same type
ADAM19 c.252-190C>A Uncertain significance ★ same type
ADAM19 c.252-193T>G Uncertain significance ★ same type
ADAM19 p.Ala241Val Uncertain significance ★ ⚠ same type
ADAM19 p.Ala24Glu Uncertain significance ★ ⚠ same type
ADAM19 p.Ala336Val 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/adam19-p-pro694ser (accessed [today's date]).

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