Is NHERF1 p.Ile320Phe (c.958A>T) pathogenic?

NHERF1 p.Ile320Phe (c.958A>T) is classified Uncertain significance in NHERF1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.084); Absent from gnomAD v4.1.

How common is NHERF1 p.Ile320Phe (c.958A>T) in the general population?

NHERF1 p.Ile320Phe (c.958A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NHERF1 p.Ile320Phe (c.958A>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

NHERF1 p.Ile320Phe

c.958A>T · rs387907537 · VCV64527

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.69	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 2.3	GERP -0.48, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 20 kb · p 0.15 · regional, not allelic
Overall
CADD	17.54	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: NHERF1
Protein: p.Ile320Phe
Coding: c.958A>T
MANE Select: NM_004252
dbSNP: rs387907537
Type: single nucleotide variant
Location: chr17:74768537 (GRCh38)
Structure: AlphaFold pLDDT 73.02 · 22 PDB
Residue 320: the 'disordered' region

Full NHERF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NHERF1 p.Ala120Val Uncertain significance ★★ ⚠ same type
NHERF1 p.Ala81Val Uncertain significance ★★ ⚠ same type
NHERF1 p.Arg151Trp Uncertain significance ★★ same type
NHERF1 p.Arg153Trp Uncertain significance ★★ ⚠ same type
NHERF1 p.Arg194Gln Uncertain significance ★★ ⚠ same type
NHERF1 p.Arg198His Uncertain significance ★★ same type
NHERF1 p.Arg270Cys Uncertain significance ★★ ⚠ same type
NHERF1 p.Arg338Cys 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/nherf1-p-ile320phe (accessed [today's date]).

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