Is IFT88 p.Met239Val (c.715A>G) pathogenic?

IFT88 p.Met239Val (c.715A>G) is classified Uncertain significance in IFT88 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.2053); Ultra-rare (popmax 0.0185%, mid).

How common is IFT88 p.Met239Val (c.715A>G) in the general population?

IFT88 p.Met239Val (c.715A>G) is ultra-rare (popmax 0.0185%, mid) (gnomAD).

What do computational predictors say about IFT88 p.Met239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.2053) — an in-silico prediction, not a clinical call.

IFT88 p.Met239Val

c.715A>G · rs201076403 · VCV1425512

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2053	likely benign
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -11.28	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 117 kb · p 0.59 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0185% Middle Eastern · 1/5,392 alleles

Filtering AF 0.00901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00666%

Overall 0.0052% 70/1,345,514 alleles · ultra-rare exomes 61/1,193,264 · genomes 9/152,250 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0185%	5,392
Admixed American	0.0173%	5,779
Remaining individualsnot grpmax-eligible	0.00753%	13,289
Ashkenazi Jewishnot grpmax-eligible	0.00732%	13,661
European (non-Finnish)	0.00565%	17,710

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: IFT88
Protein: p.Met239Val
Coding: c.715A>G
MANE Select: NM_006531
dbSNP: rs201076403
Type: single nucleotide variant
Location: chr13:20599468 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 77.20

Full IFT88 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT88 p.Ala327Thr Uncertain significance ★★ ⚠ same type
IFT88 p.Ala37Gly Uncertain significance ★★ ⚠ same type
IFT88 p.Ala458Val Uncertain significance ★★ ⚠ same type
IFT88 p.Ala510Pro Uncertain significance ★★ ⚠ same type
IFT88 p.Ala546Thr Uncertain significance ★★ ⚠ same type
IFT88 p.Ala628Ser Uncertain significance ★★ ⚠ same type
IFT88 p.Arg369His Uncertain significance ★★ ⚠ same type
IFT88 p.Arg533Trp 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/ift88-p-met239val (accessed [today's date]).

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