Is CSF1R p.Ala780Thr (c.2338G>A) pathogenic?

CSF1R p.Ala780Thr (c.2338G>A) is classified Uncertain significance in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely pathogenic (0.9921); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CSF1R p.Ala780Thr (c.2338G>A)?

CSF1R p.Ala780Thr (c.2338G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CSF1R p.Ala780Thr (c.2338G>A) in the general population?

CSF1R p.Ala780Thr (c.2338G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF1R p.Ala780Thr (c.2338G>A)?

AlphaMissense predicts likely pathogenic (score 0.9921) — an in-silico prediction, not a clinical call.

CSF1R p.Ala780Thr

c.2338G>A · VCV4840005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9921 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9921	likely pathogenic · top 5% in CSF1R
REVEL	0.724	pathogenic-leaning
SaProt	LLR -12.58	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 2,952 bp · p 1.2e-16 · regional, not allelic
Overall
CADD	18.95	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: CSF1R
Protein: p.Ala780Thr
Coding: c.2338G>A
MANE Select: NM_001288705
Type: single nucleotide variant
Location: chr5:150056323 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 780: the protein kinase domain; a UniProt-annotated variant site (in banddos); a UniProt-annotated variant site (in hdls1)

Full CSF1R 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

CSF1R p.Ala780Val Likely pathogenic ★★ same residue
CSF1R p.Ala780Pro Uncertain significance ★ ⚠ same residue
CSF1R p.Ala299Val Uncertain significance ★★ ⚠ same condition
CSF1R p.Ala770Thr Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg41Gln Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg549Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg710Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Gln173Arg 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/csf1r-p-ala780thr (accessed [today's date]).

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