Is INF2 p.Arg604Ter (c.1810C>T) pathogenic?

INF2 p.Arg604Ter (c.1810C>T) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-20). Very rare (popmax 0.0011%, sas).

How common is INF2 p.Arg604Ter (c.1810C>T) in the general population?

INF2 p.Arg604Ter (c.1810C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

INF2 p.Arg604Ter

c.1810C>T · rs1260381635 · VCV1311259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 23
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 3	GERP 6.5, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 0.000124% 2/1,612,448 alleles · very rare exomes 2/1,460,260 · genomes 0/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	8.48e-05%	1,179,806

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: INF2
Protein: p.Arg604Ter
Coding: c.1810C>T
MANE Select: NM_022489
dbSNP: rs1260381635
Type: single nucleotide variant
Location: chr14:104708510 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 604: the fh2 domain; an α-helix

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INF2 p.Arg604= Conflicting classifications of pathogenicity ★ same residue
INF2 p.Arg604Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg91Gly 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/inf2-p-arg604ter (accessed [today's date]).

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