Is FOXI1 p.Pro77= (c.231C>G) pathogenic?

FOXI1 p.Pro77= (c.231C>G) is classified Likely benign in FOXI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Rare (popmax 0.17%, afr); Associated with autosomal recessive nonsyndromic hearing loss 4.

What condition is associated with FOXI1 p.Pro77= (c.231C>G)?

FOXI1 p.Pro77= (c.231C>G) is associated with autosomal recessive nonsyndromic hearing loss 4, Pendred syndrome (ClinVar).

How common is FOXI1 p.Pro77= (c.231C>G) in the general population?

FOXI1 p.Pro77= (c.231C>G) is rare (popmax 0.17%, afr) (gnomAD).

FOXI1 p.Pro77=

c.231C>G · rs550209761 · VCV1622161

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.17%, afr)

Conditions

autosomal recessive nonsyndromic hearing loss 4

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 -12	GERP -3.8
Overall
CADD	0.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.17% African / African-American · 126/74,312 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.00806% 128/1,587,904 alleles · rare exomes 56/1,435,566 · genomes 72/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.17%	590
Remaining individualsnot grpmax-eligible	0.00163%	61,356
European (non-Finnish)	8.57e-05%	1,166,188

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: FOXI1
Protein: p.Pro77=
Coding: c.231C>G
MANE Select: NM_012188
dbSNP: rs550209761
Type: single nucleotide variant
Location: chr5:170106188 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.03

Full FOXI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Pendred syndrome

Similar variants

FOXI1 c.-18G>A Uncertain significance ★★ same condition
FOXI1 p.Ala255Thr Uncertain significance ★★ ⚠ same condition
FOXI1 p.Ala338Val Uncertain significance ★★ ⚠ same condition
FOXI1 p.Arg213Cys Uncertain significance ★★ ⚠ same condition
FOXI1 p.Arg267Gln Uncertain significance ★★ ⚠ same condition
FOXI1 p.Asn344Asp Uncertain significance ★★ ⚠ same condition
FOXI1 p.Asn66Lys Uncertain significance ★★ same condition
FOXI1 p.Asp190His Uncertain significance ★★ ⚠ same condition

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/foxi1-p-pro77 (accessed [today's date]).

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