Is CSF1R p.Pro54Ser (c.160C>T) pathogenic?

CSF1R p.Pro54Ser (c.160C>T) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.0854); Very rare (popmax 0.00267%, afr).

How common is CSF1R p.Pro54Ser (c.160C>T) in the general population?

CSF1R p.Pro54Ser (c.160C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CSF1R p.Pro54Ser (c.160C>T)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

CSF1R p.Pro54Ser

c.160C>T · VCV4775631

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -4.59	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 -0.27	GERP -4.4
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	0.027	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 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,998 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
South Asian	0.0011%	91,082

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.Pro54Ser
Coding: c.160C>T
MANE Select: NM_001288705
Type: single nucleotide variant
Location: chr5:150080914 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 54: a disulfide bond; the ig-like c2-type 1 domain; an α-helix

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

Similar variants

CSF1R p.Pro54Arg Uncertain significance ★ ⚠ same residue
CSF1R p.Pro54= Likely benign ★ same residue
CSF1R p.Pro54del Uncertain significance ★ same residue
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

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-pro54ser (accessed [today's date]).

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