Is NPHP4 p.Ala171Ser (c.511G>T) pathogenic?

NPHP4 p.Ala171Ser (c.511G>T) is classified Uncertain significance in NPHP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-26). AlphaMissense: likely benign (0.1135); No allele count reported in gnomAD v4.1 (AN 1,602,570).

How common is NPHP4 p.Ala171Ser (c.511G>T) in the general population?

NPHP4 p.Ala171Ser (c.511G>T) is no allele count reported in gnomAD v4.1 (AN 1,602,570) (gnomAD).

What do computational predictors say about NPHP4 p.Ala171Ser (c.511G>T)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

NPHP4 p.Ala171Ser

c.511G>T · rs113765431 · VCV502177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,570)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1135	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -7.23	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 -3.7	GERP -4.2
Regional constraint	o/e 1.02	unconstrained · MANE · 123 kb · p 0.49 · regional, not allelic
Overall
CADD	9.856	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

No allele count reported in gnomAD v4.1 (AN 1,602,570). 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: NPHP4
Protein: p.Ala171Ser
Coding: c.511G>T
MANE Select: NM_015102
dbSNP: rs113765431
Type: single nucleotide variant
Location: chr1:5967305 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NPHP4 p.Ala171Val Uncertain significance ★★ ⚠ same residue
NPHP4 p.Ala171Thr Benign/Likely benign ★★ same residue
NPHP4 c.2304+1G>A Pathogenic ★★ same type
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same type
NPHP4 c.2611+1G>C Pathogenic ★★ same type
NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same type
NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same type
NPHP4 c.517+1G>A 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/nphp4-p-ala171ser (accessed [today's date]).

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