Is NGFR p.Pro210Ser (c.628C>T) pathogenic?

NGFR p.Pro210Ser (c.628C>T) is classified Uncertain significance in NGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.0664); Absent from gnomAD v4.1.

How common is NGFR p.Pro210Ser (c.628C>T) in the general population?

NGFR p.Pro210Ser (c.628C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NGFR p.Pro210Ser (c.628C>T)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

NGFR p.Pro210Ser

c.628C>T · rs2071223990 · VCV2484675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 0.0027 · regional, not allelic
Overall
CADD	12.11	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: NGFR
Protein: p.Pro210Ser
Coding: c.628C>T
MANE Select: NM_002507
dbSNP: rs2071223990
Type: single nucleotide variant
Location: chr17:49510471 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.44 · 7 PDB
Residue 210: the 'disordered' region

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

Similar variants

NGFR p.Pro210= Likely benign ★ same residue
NGFR c.67-4C>T Benign ★★ same type
NGFR p.Ser132Leu Benign ★★ same type
NGFR p.Ser395= Benign/Likely benign ★★ same type
NGFR p.Thr293= Benign ★★ same type
NGFR p.Tyr111= Benign ★★ same type
NGFR p.Ala110Ser Uncertain significance ★ ⚠ same type
NGFR p.Ala229Val 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/ngfr-p-pro210ser (accessed [today's date]).

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