Is NEFH p.Arg232= (c.696C>G) pathogenic?

NEFH p.Arg232= (c.696C>G) is classified Likely benign in NEFH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-24). Very rare (popmax 0.00166%, nfe).

How common is NEFH p.Arg232= (c.696C>G) in the general population?

NEFH p.Arg232= (c.696C>G) is very rare (popmax 0.00166%, nfe) (gnomAD).

NEFH p.Arg232=

c.696C>G · rs1361674947 · VCV1568304

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00166%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -3.1, phastCons 1
Overall
CADD	16.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00166% European (non-Finnish) · 19/1,145,136 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000855%

Overall 0.00124% 19/1,530,280 alleles · very rare exomes 18/1,378,140 · genomes 1/152,140 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NEFH
Protein: p.Arg232=
Coding: c.696C>G
MANE Select: NM_021076
dbSNP: rs1361674947
Type: single nucleotide variant
Location: chr22:29480958 (GRCh38)
Gene constraint: LOEUF 1.417 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 232: the if rod domain; the 'coil 1b' region

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

Similar variants

NEFH c.1208+4A>T Uncertain significance ★★ same type
NEFH c.1209-2A>G Uncertain significance ★★ same type
NEFH p.Ala103Thr Uncertain significance ★★ same type
NEFH p.Ala141Thr Uncertain significance ★★ same type
NEFH p.Ala189Val Uncertain significance ★★ same type
NEFH p.Ala195Thr Uncertain significance ★★ same type
NEFH p.Ala203Thr Uncertain significance ★★ same type
NEFH p.Ala220Val 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/nefh-p-arg232 (accessed [today's date]).

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