Is CSF1R p.Arg919Thr (c.2756G>C) pathogenic?

CSF1R p.Arg919Thr (c.2756G>C) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-29). AlphaMissense: likely benign (0.0736); Very rare (popmax 0.004%, afr).

How common is CSF1R p.Arg919Thr (c.2756G>C) in the general population?

CSF1R p.Arg919Thr (c.2756G>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CSF1R p.Arg919Thr (c.2756G>C)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

CSF1R p.Arg919Thr

c.2756G>C · rs922508428 · VCV1952378

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.71	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 1	GERP -1.7, phastCons 0.001
Regional constraint	o/e 1.08	unconstrained · MANE · 279 bp · p 0.48 · regional, not allelic
Overall
CADD	15.75	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 0.004% African / African-American · 3/75,046 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000342% 5/1,461,872 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,015
European (non-Finnish)	0.000169%	590,019

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.Arg919Thr
Coding: c.2756G>C
MANE Select: NM_001288705
dbSNP: rs922508428
Type: single nucleotide variant
Location: chr5:150054329 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 919: the 'disordered' region; 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-arg919thr (accessed [today's date]).

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