Is ADAM19 p.Ser753Phe (c.2258C>T) pathogenic?

ADAM19 p.Ser753Phe (c.2258C>T) is classified Uncertain significance in ADAM19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.155); Absent from gnomAD v4.1.

How common is ADAM19 p.Ser753Phe (c.2258C>T) in the general population?

ADAM19 p.Ser753Phe (c.2258C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAM19 p.Ser753Phe (c.2258C>T)?

AlphaMissense predicts likely benign (score 0.155) — an in-silico prediction, not a clinical call.

ADAM19 p.Ser753Phe

c.2258C>T · VCV3827974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.155 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.155	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -7.75	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 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.31 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAM19
Protein: p.Ser753Phe
Coding: c.2258C>T
MANE Select: NM_033274
Type: single nucleotide variant
Location: chr5:157489169 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.93
Residue 753: the 'disordered' region

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-ser753phe (accessed [today's date]).

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