Is DLD p.Phe106Ile (c.316T>A) pathogenic?

DLD p.Phe106Ile (c.316T>A) is classified Uncertain significance in DLD (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6534); Very rare (popmax 0.00402%, afr).

How common is DLD p.Phe106Ile (c.316T>A) in the general population?

DLD p.Phe106Ile (c.316T>A) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about DLD p.Phe106Ile (c.316T>A)?

AlphaMissense predicts likely pathogenic (score 0.6534) — an in-silico prediction, not a clinical call.

DLD p.Phe106Ile

c.316T>A · rs1242981665 · VCV1050625

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6534	likely pathogenic
REVEL	0.26	benign-leaning
SaProt	LLR -15.06	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	26.5	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 0.00402% African / African-American · 3/74,596 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000188% 3/1,597,846 alleles · very rare exomes 1/1,445,640 · genomes 2/152,206 · 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: DLD
Protein: p.Phe106Ile
Coding: c.316T>A
MANE Select: NM_000108
dbSNP: rs1242981665
Type: single nucleotide variant
Location: chr7:107903526 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 106: an α-helix

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

Similar variants

DLD c.1464+1G>A Pathogenic/Likely pathogenic ★★ same type
DLD c.198+1G>T Likely pathogenic ★★ same type
DLD c.39+1G>A Likely pathogenic ★★ same type
DLD c.40-2A>G Likely pathogenic ★★ same type
DLD c.583-1G>C Likely pathogenic ★★ same type
DLD c.684+1G>T Likely pathogenic ★★ same type
DLD c.875+1G>A Pathogenic/Likely pathogenic ★★ same type
DLD p.Arg315Ter 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/dld-p-phe106ile (accessed [today's date]).

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