Is POLB p.Ser171Phe (c.512C>T) pathogenic?

POLB p.Ser171Phe (c.512C>T) is classified Uncertain significance in POLB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely benign (0.2932); No allele count reported in gnomAD v4.1 (AN 1,581,266).

How common is POLB p.Ser171Phe (c.512C>T) in the general population?

POLB p.Ser171Phe (c.512C>T) is no allele count reported in gnomAD v4.1 (AN 1,581,266) (gnomAD).

What do computational predictors say about POLB p.Ser171Phe (c.512C>T)?

AlphaMissense predicts likely benign (score 0.2932) — an in-silico prediction, not a clinical call.

POLB p.Ser171Phe

c.512C>T · rs2488011051 · VCV3216304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2932 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,581,266)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2932	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -12.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 0.0028 · regional, not allelic
Overall
CADD	25.1	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

No allele count reported in gnomAD v4.1 (AN 1,581,266). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: POLB
Protein: p.Ser171Phe
Coding: c.512C>T
MANE Select: NM_002690
dbSNP: rs2488011051
Type: single nucleotide variant
Location: chr8:42357354 (GRCh38)
Gene constraint: LOEUF 1.772 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 94.30 · 435 PDB

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

Similar variants

POLB p.Ala185Thr Uncertain significance ★ ⚠ same type
POLB p.Ala23Ser Uncertain significance ★ ⚠ same type
POLB p.Arg254Ile Uncertain significance ★ ⚠ same type
POLB p.Glu129Gly Uncertain significance ★ ⚠ same type
POLB p.Glu316Lys Uncertain significance ★ ⚠ same type
POLB p.Glu335Lys Uncertain significance ★ ⚠ same type
POLB p.His212Tyr Uncertain significance ★ ⚠ same type
POLB p.Ile119Val 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/polb-p-ser171phe (accessed [today's date]).

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