Is CSF1R p.Tyr154= (c.462C>T) pathogenic?

CSF1R p.Tyr154= (c.462C>T) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-20). Very rare (popmax 0.0011%, sas).

How common is CSF1R p.Tyr154= (c.462C>T) in the general population?

CSF1R p.Tyr154= (c.462C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CSF1R p.Tyr154=

c.462C>T · rs760292683 · VCV2054107

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.66	GERP -3.6, phastCons 0.99
Overall
CADD	5.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,092 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,736 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asiangrpmax	0.0011%	91,092
European (non-Finnish)	0.000763%	131,118

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr154=
Coding: c.462C>T
MANE Select: NM_001288705
dbSNP: rs760292683
Type: single nucleotide variant
Location: chr5:150080182 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 154: a β-strand; a disulfide bond; the ig-like c2-type 2 domain

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-tyr154 (accessed [today's date]).

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