Is CSF1R p.Phe577Ile (c.1729T>A) pathogenic?

CSF1R p.Phe577Ile (c.1729T>A) is classified Uncertain significance in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely pathogenic (0.9206); Very rare (popmax 8.47e-05%, nfe).

How common is CSF1R p.Phe577Ile (c.1729T>A) in the general population?

CSF1R p.Phe577Ile (c.1729T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CSF1R p.Phe577Ile (c.1729T>A)?

AlphaMissense predicts likely pathogenic (score 0.9206) — an in-silico prediction, not a clinical call.

CSF1R p.Phe577Ile

c.1729T>A · rs1757539157 · VCV1419854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9206	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 1,956 bp · p 6.2e-07 · regional, not allelic
Overall
CADD	27.7	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 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.2e-05% 1/1,614,098 alleles · very rare exomes 1/1,461,888 · genomes 0/152,210 · 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: CSF1R
Protein: p.Phe577Ile
Coding: c.1729T>A
MANE Select: NM_001288705
dbSNP: rs1757539157
Type: single nucleotide variant
Location: chr5:150061747 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 577: a UniProt-annotated variant site (in banddos)

Full CSF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF1R p.Ala780Val Likely pathogenic ★★ same type
CSF1R p.Ala781Val Pathogenic ★★ same type
CSF1R p.Arg676Ter Pathogenic ★★ same type
CSF1R p.Arg777Gln Pathogenic ★★ same type
CSF1R p.Arg777Trp Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Gln481Ter Pathogenic ★★ 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/csf1r-p-phe577ile (accessed [today's date]).

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