Is USH2A p.Ser1007Thr (c.3019T>A) pathogenic?

USH2A p.Ser1007Thr (c.3019T>A) is classified Uncertain significance in USH2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-26). AlphaMissense: likely benign (0.1166); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with USH2A p.Ser1007Thr (c.3019T>A)?

USH2A p.Ser1007Thr (c.3019T>A) is associated with Inborn genetic diseases (ClinVar).

How common is USH2A p.Ser1007Thr (c.3019T>A) in the general population?

USH2A p.Ser1007Thr (c.3019T>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about USH2A p.Ser1007Thr (c.3019T>A)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

USH2A p.Ser1007Thr

c.3019T>A · rs371711993 · VCV2184594

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.43	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 3.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	20.3	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 0.000678% European (non-Finnish) · 8/1,179,362 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,158 alleles · very rare exomes 8/1,460,892 · genomes 0/152,266 · joint denominator

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: USH2A
Protein: p.Ser1007Thr
Coding: c.3019T>A
MANE Select: NM_206933
dbSNP: rs371711993
Type: single nucleotide variant
Location: chr1:216217525 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1007: the laminin egf-like 10 domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH2A p.Ser1007= Likely benign ★ same residue
USH2A p.Gln4900Ter Pathogenic/Likely pathogenic ★★ same condition
USH2A p.Ala1617Val Uncertain significance ★★ same condition
USH2A p.Ala1877Glu Uncertain significance ★★ same condition
USH2A p.Ala1952Val Uncertain significance ★★ ⚠ same condition
USH2A p.Ala2111Glu Uncertain significance ★★ ⚠ same condition
USH2A p.Ala2234Val Uncertain significance ★★ ⚠ same condition
USH2A p.Ala2246Asp Uncertain significance ★★ ⚠ same condition

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/ush2a-p-ser1007thr (accessed [today's date]).

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