Is TLN1 p.Asp1626Val (c.4877A>T) pathogenic?

TLN1 p.Asp1626Val (c.4877A>T) is classified Uncertain significance in TLN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.7788); Absent from gnomAD v4.1.

How common is TLN1 p.Asp1626Val (c.4877A>T) in the general population?

TLN1 p.Asp1626Val (c.4877A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TLN1 p.Asp1626Val (c.4877A>T)?

AlphaMissense predicts likely pathogenic (score 0.7788) — an in-silico prediction, not a clinical call.

TLN1 p.Asp1626Val

c.4877A>T · VCV4595520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7788 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7788	likely pathogenic
REVEL	0.739	pathogenic-leaning
SaProt	LLR -13.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	26.7	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

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: TLN1
Protein: p.Asp1626Val
Coding: c.4877A>T
MANE Select: NM_006289
Type: single nucleotide variant
Location: chr9:35707150 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 4 PDB
Residue 1626: the 'interaction with synm' region; the 'interaction with vcl and f-actin' region; the 'helical bundle r7b' region

Full TLN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TLN1 c.1206+7A>G Likely benign ★★ same type
TLN1 c.2459-5C>T Benign ★★ same type
TLN1 p.Ala1545= Benign ★★ same type
TLN1 p.Ala1821= Benign ★★ same type
TLN1 p.Leu778= Benign ★★ same type
TLN1 p.Pro1740= Benign ★★ same type
TLN1 p.Thr1029= Benign ★★ same type
TLN1 p.Thr1867= 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/tln1-p-asp1626val (accessed [today's date]).

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