Is CSF2RB p.Ser165Phe (c.494C>T) pathogenic?

CSF2RB p.Ser165Phe (c.494C>T) is classified Uncertain significance in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-12). AlphaMissense: likely benign (0.1677); Absent from gnomAD v4.1.

How common is CSF2RB p.Ser165Phe (c.494C>T) in the general population?

CSF2RB p.Ser165Phe (c.494C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2RB p.Ser165Phe (c.494C>T)?

AlphaMissense predicts likely benign (score 0.1677) — an in-silico prediction, not a clinical call.

CSF2RB p.Ser165Phe

c.494C>T · rs1217163540 · VCV1993318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1677	likely benign
REVEL	0.433	indeterminate
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.41, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 0.00014 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CSF2RB
Protein: p.Ser165Phe
Coding: c.494C>T
MANE Select: NM_000395
dbSNP: rs1217163540
Type: single nucleotide variant
Location: chr22:36929504 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.50 · 10 PDB
Residue 165: the fibronectin type-iii 1 domain

Full CSF2RB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF2RB p.Ser165= Likely benign ★ same residue
CSF2RB p.Ala185Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala255Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Val Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala394Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala455Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala576Thr Uncertain significance ★★ ⚠ 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/csf2rb-p-ser165phe (accessed [today's date]).

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